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Introduction: Repetitive transcranial magnetic stimulation (rTMS) shows promise in treating neuropsychological disorders. This systematic review and meta-analysis investigated the effects of rTMS on inflammatory cytokines and brain-derived neurotrophic factor (BDNF) under these conditions., Method: We searched five electronic databases for relevant studies. Twelve studies (six randomized controlled trials [RCTs] and six cohort studies) were included in the systematic review, with six RCTs included in the meta-analysis. The primary outcome was tumor necrosis factor-alpha (TNF-α) levels, with secondary outcomes including interleukin-6 (IL-6), interleukin-1 beta (IL-1β), high-sensitivity C-reactive protein (hs-CRP), interferon-gamma (IFN-γ), and BDNF., Results: Meta-analysis revealed a significant decrease in TNF-α levels after rTMS (weighted mean difference [WMD]: -6.65, 95% confidence interval [CI]: -10.47-2.83, p < 0.05), with greater effects associated with longer interventions. No significant change was found in the IL-6 levels. BDNF levels increased significantly (WMD: 7.97, 95% CI: 2.8-13.15, p < 0.05). Qualitative synthesis indicated consistent reductions in IL-1β. High heterogeneity was observed in some analyses., Conclusion: rTMS may exert therapeutic effects on neuropsychological disorders partly through modulating neuroinflammation and promoting neuroplasticity. However, high heterogeneity and study limitations necessitate larger, more standardized clinical trials to confirm these effects and explore their clinical significance., (© 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Aim: Methamphetamine use disorders (MUDs) cause widespread disruptions in metabolomic and immunologic processes, highlighting the need for new therapeutic approaches. The purpose of this study was to find molecular and neuroimaging biomarkers for methamphetamine addiction., Methods: In this study, we recruited 231 patients with MUD at varying stages of withdrawal and 40 healthy controls to quantify the blood levels of 52 molecules using enzyme-linked immunosorbent assay., Results: The overall molecular disruption caused by methamphetamine was inversely related to withdrawal time (P = 0.0008), with partial recovery observed after 1 year of follow-up (P = 2.20 × 10 -5 ). Molecules related to stress, immune activation, oxidative products, and cardiac injury were significantly elevated in all MUD groups, while antioxidation enzymes were downregulated. Additionally, the blood level of brain-derived neurotrophic factor was significantly correlated with gray matter volumes in nine brain regions (fusiform gyrus, orbitofrontal cortex, temporal pole, caudate, cerebellum crus, and vermis, adjusted P < 0.05) among patients with MUD., Conclusion: These findings suggest that patients with MUD exhibit elevated levels of immune response, stress, and oxidative stress, which are associated with brain structural abnormalities., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences © 2024 Japanese Society of Psychiatry and Neurology.)

Objectives: Exercise might restore morphine-induced behavioural and molecular changes, but related evidence is inconsistent. We conducted a systematic review and meta-analysis of animal studies to elucidate the contribution of brain-derived neurotrophic factor (BDNF) to exercise effects on morphine addiction., Methods: We searched papers published until May 25, 2024, in databases, manually searched related references, screened eligible studies, and extracted relevant data. The risk of bias was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE)'s risk bias tool. Subsequently, we summarised study characteristics, reported risks of bias, and conducted a meta-analysis. Subgroup and sensitivity analyses were also conducted., Results: The meta-analysis showed that exercise increased BDNF levels in morphine-addicted male animals, regardless of the exercise type and intensity. Under morphine addiction, voluntary exercise (running wheel) affected BDNF levels in males, whilst forced exercise (treadmill exercise) did not. Furthermore, different exercise intensities did not affect BDNF levels in males. The sensitivity analysis determined that the results were robust., Conclusions: Exercise increased BDNF levels in male but not in female animals. BDNF level changes might be related to the type of exercise but not its intensity. Therefore, BDNF might serve as a biomarker for the effects of different exercise types.

Background: Peripheral levels of brain-derived neurotrophic factor (BDNF) are often used as a biomarker for the rapid plasticity-promoting effects of ketamine, psychedelics, and other psychoplastogens in humans. However, studies analyzing peripheral BDNF after psychoplastogen exposure show mixed results. In this meta-analysis, we aimed to test whether the rapid upregulation of neuroplasticity seen in preclinical studies is detectable using peripheral BDNF in humans., Methods: This analysis was pre-registered (PROSPERO ID: CRD42022333096) and funded by the University of Fribourg. We systematically searched PubMed, Web of Science, and PsycINFO to meta-analyze the effects of all available psychoplastogens on peripheral BDNF levels in humans, including ketamine, esketamine, LSD, psilocybin, ayahuasca, DMT, MDMA, scopolamine, and rapastinel. Risk of bias was assessed using Cochrane Risk of Bias Tools. Using meta-regressions and mixed effects models, we additionally analyzed the impact of several potential moderators., Results: We included 29 studies and found no evidence that psychoplastogens elevate peripheral BDNF levels in humans (SMD = 0.024, p = 0.64). This result was not affected by drug, dose, blood fraction, participant age, or psychiatric diagnoses. In general, studies with better-controlled designs and fewer missing values reported smaller effect sizes. Later measurement timepoints showed minimally larger effects on BDNF., Conclusion: These data suggest that peripheral BDNF levels do not change after psychoplastogen administration in humans. It is possible that peripheral BDNF is not an informative marker of rapid changes in neuroplasticity, or that preclinical findings on psychoplastogens and neuroplasticity may not translate to human subjects. Limitations of this analysis include the reliability and validity of BDNF measurement and low variation in some potential moderators. More precise methods of measuring rapid changes in neuroplasticity, including neuroimaging and stimulation-based methods, are recommended for future studies attempting to translate preclinical findings to humans., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Previous studies have reported conflicting findings regarding the efficacy of esketamine in managing postoperative depression. While the positive effects of subanesthetic doses esketamine have been observed in treatment-resistant depression, the response to this medication in patients experiencing depression following surgery has not been consistent. Building upon the known impact of anesthesia on brain function, we have formulated a hypothesis suggesting that the timing of esketamine administration in relation to anesthesia may significantly affect its efficacy in managing postoperative depression. The aim of this study was to investigate the effect of esketamine administered at different time points before and after anesthesia., Methods: Our randomized, double-blind, controlled study involved 120 patients undergoing laparoscopic bariatric surgery, randomly divided into three groups. Group Post- ESK received an intravenous injection of esketamine at a dose of 0.2 mg/kg after anesthesia induction. Group Pre- ESK received the same esketamine dosage 2 h prior to anesthesia induction. Group Placebo served as the control group and received a 0.9% saline solution after induction. The primary outcome measures of the study were depression scores as measured by Patient Health Questionnaire-9 (PHQ-9) and plasma brain-derived neurotrophic factor (BDNF) levels., Results: On the first postoperative day, the PHQ-9 scores, incidence and severity of postoperative depression in the Pre-ESK group were significantly lower than those in the Post-ESK and placebo groups (P < 0.05). Additionally, plasma BDNF levels in the Pre-ESK group were significantly higher than those in the Post-ESK and placebo groups (P < 0.05). Notably, there was a negative correlation between PHQ-9 scores and plasma BDNF levels., Conclusions: Our study supports the potential for subanesthetic dose esketamine to alleviate postoperative depression symptoms following laparoscopic bariatric surgery, and anesthetic drugs have a significant effect on its efficacy. The use of subanesthetic dose esketamine after anesthesia does not improve postoperative depression symptoms in patients undergoing laparoscopic bariatric surgery, while the use of sub-anesthetic dose esketamine before anesthesia can improve postoperative depression symptoms., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Introduction: The aim of the study was to assess the predicting value of neuromarkers for psychomotor performances of congenital heart defect (CHD) patients before surgery, as until now the researchers only evaluated neuromarkers after the surgical treatment of the CHD., Methods: This cross-sectional study included children with CHD who did not receive treatment (interventional or cardiac surgery). Psychomotor development was evaluated using the Denver II Screening Test. Blood samples were collected for neuromarkers analysis: neuron-specific enolase (NSE), protein S100 (pS100), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP)., Results: We enrolled 77 children. Patients with CHD experienced more frequent developmental delays compared to healthy children (12-34% in the non-cyanotic group and 26-74% in the cyanotic group). The association between type of CHD and psychomotor impairment was statistically significant (p < 0.0001, RR = 2.604, CI = 2.07-3.26). Neuromarkers value was compared between cyanotic and non-cyanotic groups: NSE and BDNF values were higher in the cyanotic group, respectively, pS100 and GFAP had slightly higher values in the non-cyanotic group. A correlation coefficient of 0.35 (p = 0.023) was obtained between psychomotor development and BDNF level. An AUC of 0.72 was obtained for psychomotor development and BDNF in ROC analysis with the cut-off value of 5895 pg/ml., Conclusion: BDNF is showing moderate discriminative ability in predicting psychomotor development outcomes in pediatric patients with CHD., (© 2024 The Author(s). International Journal of Developmental Neuroscience published by Wiley Periodicals LLC on behalf of International Society for Developmental Neuroscience.)

Parkinson's disease (PD) neuropathology is marked by the selective loss of dopaminergic neurons in the substantia nigra pars compacta, accompanied by the widespread involvement of central and peripheral structures. Brain-derived neurotrophic factor (BDNF), a neurotrophin crucial for the survival of dopaminergic neurons, plays a pivotal role in neuronal and glial development, neuroprotection, and the modulation of synaptic plasticity. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive technique, enhances neurotransmitter release, trans-synaptic efficacy, signaling pathways, gene transcription, neuroplasticity, and neurotrophism. Evidence supports that high-frequency rTMS increases BDNF expression and improves task-specific cognitive deficits in PD patients. This article outlines a detailed protocol to investigate whether rTMS targeting the dorsolateral prefrontal cortex bilaterally induces changes in plasma BDNF levels, the plasma-derived exosomal BDNF concentration, and executive functions in individuals with PD. Identifying non-invasive interventions that effectively modulate the neurobiological mechanisms underlying cognitive and behavioral functions is critical for addressing cognitive impairments and mitigating disease progression in the PD population. This study aims to advance translational research by identifying biomarkers and developing therapeutic strategies for future applications in neurodegenerative diseases.

Background: Klotho and neurotrophic factors, including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF), have been shown to play a role in cognitive functions. However, these molecules have not been investigated in bipolar disorder simultaneously to assess the interactions among them and their relationships with cognitive functions. This study investigated the relationships among cognitive function, klotho, and neurotrophic factors in patients with bipolar disorder in the remission period., Methods: Male, bipolar disorder (BD) patients (patient group, n = 48) in the remission period and healthy volunteers (control group, n = 48) were included in the study. The Stroop test and Wechsler Memory Scale-Visual Production Subtest were applied, and the serum levels of Klotho, BDNF, GDNF, and NGF were measured with an ELISA reader., Results: The klotho protein levels (0.12 ± 0.15 and 0.17 ± 0.16) and NGF levels (34.36 ± 41.99 and 48.54 ± 41.06) in the patient group were significantly lower than those in the control group (Z = -3.071, p = 0.002 and Z = -2.217, p = 0.027, respectively). In the patient group, there was a positive correlation between the klotho and NGF levels (p = 0.003, r s  = 0.413), and a negative correlation was detected between the NGF and GDNF levels (p = 0.013, r s  = -0.355). Klotho and NGF were predictors of Weshler 40-min test results (adjusted R2 = 0.467), and Klotho and BDNF were predictors of Stroop test colour word reading time (adjusted R2 = 0.391) with other variables., Conclusion: In BD patients, klotho, BDNF, GDNF and NGF are associated with cognitive functions and exhibit different characteristics from those of the control group. Nevertheless, the differences related to these molecules seem to be associated with a regulatory system rather than merely an increase or decrease in serum levels., Competing Interests: Declarations. Ethics approval and consent to participate: We confirm that ethical approval has been granted under approval number E-16214662–050.01.04–198306-150, reference number is, and we obtained written informed consent from the participants accordingly. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: This study investigated the longitudinal associations between serum BDNF (sBDNF) levels measured early after injury and the onset of post-traumatic stress disorder (PTSD) across two years., Methods: Patients with moderate to severe physical injuries were enrolled from a trauma center. At baseline, sBDNF levels were measured and a comprehensive socio-demographic and clinical data were collected. The range of time from physical injuries to blood collection was 1-28 days, with a median (IQR) of 8.0 (6.0) days. PTSD diagnoses were determined at 3, 6, 12, and 24 months post-injury using the CAPS-5. Linear regression analyses assessed the relationship between sBDNF levels and PTSD diagnoses., Results: Out of 923 patients, 112 (12.1 %) developed PTSD during the study. Prevalence rates were 8.8 % at 3 months, 7.6 % at 6 months, 4.8 % at 12 months, and 3.7 % at 24 months. Significantly, lower sBDNF levels were associated with PTSD at 12 and 24 months, after adjusting for covariates and applying Bonferroni corrections, but not at earlier assessments., Limitations: Focusing on patients with moderate to severe injuries from a single center may limit the findings' generalizability., Conclusion: Early post-injury sBDNF levels are predictive biomarkers for PTSD, especially significant at 12 and 24 months post-injury., Competing Interests: Declaration of competing interest Jae-Min Kim declares research support in the last 5 years from Janssen and Lundbeck. Sung-Wan Kim declares research support in the last 5 years from Janssen, Boehringer Ingelheim, Allergan and Otsuka. All other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: BDNF has increasingly gained attention as a key molecule controlling remyelination with a prominent role in neuroplasticity and neuroprotection. Still, it remains unclear how BDNF relates to clinicoradiological characteristics particularly at the early stage of the disease where precise prognosis for the further MS course is crucial., Methods: BDNF, NfL and GFAP concentrations in serum and CSF were assessed in 106 treatment naïve patients with MS (pwMS) as well as 73 patients with other inflammatory/non-inflammatory neurological or somatoform disorders using a single molecule array HD-1 analyser. PwMS were evaluated for highly active profiles by applying the aggressive disease course criteria proposed by ECTRIMS. Serum/CSF values were logarithmically transformed and compared across groups using one-way ANOVA, while correlations were calculated using Pearson's correlations. ROC analysis and AUC comparisons for diagnostic performance of the three biomarkers were computed in an explorative analysis., Results: Serum BDNF (sBDNF) concentrations were higher in treatment naïve pwMS with disease onset after the age of 40 years (p = 0.029), in pwMS with ≥2 gadolinium-enhancing lesions (p = 0.009) and with motor, cerebellar, cognitive or sphincter symptoms at onset (p = 0.036). BDNF correlated positively with NfL (r = 0.198, p = 0.014) and GFAP (r = 0.253, p = 0.002) in serum, but not in CSF. Neurological patients with an acute inflammatory relapse showed significantly higher sBDNF levels (p = 0.03) compared to somatoform controls, while patients without acute relapse did not differ from somatoform controls (p = 0.4). Better diagnostic performance was found for sBDNF than sNfL and sGFAP in differentiating between patients with vs. without 2 or more gadolinium-enhancing lesions (p < 0.05) and for sBDNF as compared to sNfL for separating patients with disease onset after vs. before age of 40 years., Conclusion: In pwMS, BDNF serum levels differ depending on disease-related characteristics, suggesting that not only inflammatory activity but also remyelination capacities may vary with disease severity. BDNF is increased when other biomarkers of neuroaxonal damage and neurodegeneration, such as NfL and GFAP, are elevated, possibly as a compensatory mechanism, and reflect possibly further pathophysiological aspects in MS beyond NfL and GFAP, probably including an apoptotic role for BDNF in neuroinflammation., Competing Interests: Declarations. Conflicts of interest: JHS reports travel reimbursement from Bayer AG. CF reports speaker honoraria and honoraria for participating in advisory boards from Alexion, Bristol Myers Squibb, Novartis, Teva, Merck, Sanofi Genzyme and Roche, and received research support from Novartis and Sanofi Genzyme. YY has been supported by travel grants from Novartis and Sanofi Genzyme and has received honoraria for active participation in advisory boards and speaker/writing honoraria by Bristol Meyers Squibb, Kassenärztliche Vereinigung Hessen, Landesärztekammer Hessen, Merck, Novartis, RG Gesellschaft für Information und Organisation mbH, Roche, Sanofi Genzyme, TEVA. His research is funded by Novartis. SB received honoraria from Biogen Idec, Bristol Meyer Squibbs, Hexal, Merck Healthcare, Mylan, Novartis, Roche, Sanofi Genzyme and TEVA and his research is supported by the Deutsche Forschungsgemeinschaft (DFG, SFB CRC-TR-128 and CRC-TR-355) and the Hermann and Lilly Schilling Foundation. MM, KK, KW, MSP, MH, FS, JJ, LF, VA report no conflicts of interest., (© 2024. The Author(s).)

Curcumin is known for its potential health benefits; however, the evidence remains inconclusive regarding its necessity as a supplement for athletes during the preparatory phase of training. This study aimed to assess the effect of 6-week curcumin supplementation at a dose of 2g/day on selected inflammatory markers, blood count, and brain-derived neurotropic factor (BDNF) levels in middle-aged amateur long-distance runners during the preparatory period of a macrocycle. Thirty runners were randomly assigned to either a curcumin-supplemented group (CUR, n = 15) or a placebo group (PLA, n = 15). Venous blood samples were collected at rest, immediately post-exercise, and 1h post-exercise. The participants underwent a graded exercise stress test, with an increasing inclination angle after reaching a speed of 14 km/h, both before and after the 6-week supplementation period. Blood samples were collected at rest, 3 minutes post-stress test, and after 1 hour of recovery. The results showed no significant changes in C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interleukin-1 β (IL-1β), or blood morphology due to curcumin supplementation. However, BDNF levels increased by 21% in the CUR group post-supplementation, while a 5% decrease was observed in the PLA group. These findings do not support a significant effect of curcumin supplementation on inflammatory markers, blood count, or BDNF concentration. Further research is warranted to determine the potential benefits of curcumin supplementation for endurance athletes during the preparatory period for a training cycle., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Bańkowski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Brain-derived neurotrophic factor (BDNF) is implicated in the etiology of schizophrenia, and peripheral BDNF levels are affected by the short-term antipsychotic treatment. However, the data on their long-term effects on BDNF levels are scarce, and there is no information whether BDNF levels change during sustained remission in relation to values in healthy individuals. The aim of the present study was to compare serum BDNF levels in patients in long-term remission and healthy controls. This study is an extension of our previous research on the effects of olanzapine and risperidone on serum BDNF in acute-episode patients with schizophrenia. Patients who remained in remission for at least 3 years on the same antipsychotic regimen (40 % of the initial cohort) were included. Symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Serum BDNF levels were measured by ELISA in patients in remission (N = 20), evaluated at baseline, after 6 weeks of treatment and after 3 years of treatment, and in healthy individuals (N = 40). At baseline (p = 0.046) and after 6 weeks of treatment (p = 0.028), patients had significantly lower BDNF levels than controls. However, after 3 years of continuous antipsychotic maintenance treatment, serum BDNF levels were increased compared to baseline and values after 6 weeks of treatment in remitted patients, and were also significantly higher in patients than in healthy controls (p = 0.002). Antipsychotic medications appear to have distinct effects on serum BDNF levels in short-and long-term treatment. It remains to be determined if such finding may be related to potential neuroprotective effects of antipsychotic maintenance treatment., Competing Interests: Declaration of competing interest The authors declare no financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2025 Elsevier Inc. All rights reserved.)

While molecular adaptations accompanying neuroplasticity during physical exercises are well-established, little is known about adaptations during dysphagia-targeted exercises. This research article has two primary purposes. First, we aim to review the existing literature on the intersection between resistance (strength) training, molecular markers of neuroplasticity, and dysphagia rehabilitation. Specifically, we discuss the molecular mechanisms of two potential molecular markers: brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) in exercise-induced neuroplasticity. Second, we present preliminary data on the effects of two weeks of detraining on circulating serum BDNF, IGF-1 levels, and expiratory muscle strength. This subset is a part of our more extensive studies related to dysphagia-targeted resistance exercise and neuroplasticity. Five young adult males underwent four weeks of expiratory muscle strength training, followed by two weeks of detraining. We measured expiratory strength, circulating levels of BDNF, and IGF-1 at post-training and detraining conditions. Our results show that expiratory muscle strength, serum BDNF, and IGF-1 levels decreased after detraining; however, this effect was statistically significant only for serum BDNF levels. Oropharyngeal and upper airway musculature involved in swallowing undergoes similar adaptation patterns to skeletal muscles during physical exercise. To fully comprehend the mechanisms underlying the potential neuroplastic benefits of targeted exercise on swallowing functions, mechanistic studies (models) investigating neuroplasticity induced by exercises addressing dysphagia are critical. Such models would ensure that interventions effectively and efficiently achieve neuroplastic benefits and improve patient outcomes, ultimately advancing our understanding of dysphagia-targeted exercise-induced neuroplasticity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Diabetes mellitus and depression are comorbidities that can be caused by each other. Brain-derived neurotrophic factor (BDNF) functions as a neuronal growth factor. It maintains the functional integrity of the nervous system., Aim: To study the possible association between BDNF levels and gene polymorphism with depression in patients diagnosed with type 2 diabetes mellitus., Methods: The Elisa technique measured BDNF, and rs6265 gene polymorphism was detected using real-time PCR. Depression was assessed utilizing a clinical interview tool designed to establish the diagnosis of depression and differentiate it from other psychiatric diseases., Results: BDNF levels were significantly lower in patients with type 2 diabetes mellitus and symptoms of depression than in patients with type 2 diabetes mellitus and no symptoms of depression (82.6±16.1. vs. 122± 17.47, P< 0.001). There was a statistically significant difference in BDNF levels in patients with diabetes among the three genotypes of the BDNF gene (P-value < 0.001). Val/ Val carriers had the highest serum BDNF levels, and Met/ Met carriers had the lowest serum BDNF levels. Subgroup analysis showed statistically significant genotype-related differences in serum BDNF levels among the three subgroups in the Depression group. Val/ Val carriers had the highest serum BDNF levels, and Met/ Met carriers had the lowest serum BDNF levels. BDNF Val66Met polymorphism had no significant association with the presence of depression, yet there was a trend towards significance (p = 0.05)., Conclusion: In this pilot, Low levels of BDNF were associated with depression in patients with type 2 diabetes. Carriers of the Met/ Met allele have the lowest serum BDNF levels. Multicenter studies with more participants are required., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Examine the cardiovascular, muscular function, cognitive, and neural plastic responses to determine the safety and effectiveness of acute Intermittent hypoxia (AIH) at a low, high, and control fractional inspired oxygen (FiO 2 ) dosage METHODS: Thirteen human participants performed 30-min of AIH in 60-s intervals at FiO2's of 0.21 (AIH 21 ), 0.15 (AIH 15 ), and 0.09 (AIH 9 ). Heart rate variability (root mean squared of successive differences; RMSSD), heart rate, oxygen saturation (SpO2), blood pressure, muscular strength, neuromuscular activation, cerebral hemodynamic responses, cognition, symptomology, and brain-derived neurotrophic factor (BDNF) responses were measured before (Pre-AIH), after (post-AIH), and at 20-min of recovery (Recovery-AIH) RESULTS: There were no differences between AIH protocols for heart rate, RMSSD, blood pressure, or SpO2. Muscular strength improved Post-AIH for AIH 15 (10 %) and AIH 9 (14 %) and remained elevated (6 %) at Recovery-AIH. Neuromuscular activation increased Pre-AIH to Post-AIH for AIH15 (10 %) and AIH 9 (11 %). Cerebral hemodynamic responses were not impacted between conditions. Both AIH 15 and AIH9 increased BDNF Post-AIH (62 %) and Recovery-AIH (63 %) CONCLUSION: Acute intermittent hypoxia is generally safe and effective at producing neural plastic responses, but further examination of co-occurring cardiovascular diseases is needed. This study provides safety focused findings which will widen the adoption and refinement of AIH protocols., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This systematic review with meta-analysis investigated the effects of exercise training on brain-derived neurotrophic factor (BDNF) in older adults. Electronic databases of PubMed, Web of Science and Scopus were searched for studies investigating the effect of exercise training ≥4 weeks on resting BDNF levels in older adults. A standardized mean difference (SMD) was generated through random effects model. Thirty-five randomized-controlled trials met the inclusion criteria. Exercise training significantly increased resting BDNF levels [SMD = 0.56 (95 % CI 0.28 to 0.85)] both in plasma (SMD = 0.63) and serum (SMD = 0.54). Regarding exercise modality, aerobic (SMD = 0.48), resistance (SMD = 0.76) and combined exercise training (SMD = 0.55) increased BDNF levels. Exercise training with the duration of 12 weeks (SMD =0.65), moderate-to-vigorous (SMD = 0.83) and vigorous intensity (SMD = 0.71), and 3-4 sessions per week frequency (SMD = 0.78) yielded the largest effects on BDNF elevation. Since BDNF represents a fundamental contribution in neuronal processes and is linked to brain health, exercise training may help delay aging-related neuro-degenerative processes. REGISTRATION NUMBER: CRD42024499195., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cognitive dysfunction is prevalent but inadequately treated in people with multiple sclerosis (PwMS). Central vestibular functions are associated with multiple cognitive domains in PwMS, even when controlling for disability status. To our knowledge, the effectiveness of vestibular training on cognition in PwMS has never been explored. The study's purpose was to determine the effect of vestibular training on PwMS's cognitive functions., Methods: Forty PwMS with relapsing-remitting MS, primarily fatigued, were randomly divided into two equal groups. The control group (GI) was treated with aerobic endurance exercises using stationary bicycle training. The study group (GII) was treated with aerobic endurance exercises as GI in addition to a designed vestibular training program. Outcome measures of cognition were assessed pre- and post-treatment using the Arabic version of Brief International Cognitive Assessment for MS (BICAMS-A) and serum Brain-derived neurotrophic factor (BDNF)., Results: Post-treatment, there was a significant increase of oral Symbol Digit Modalities Test (SDMT), California Verbal Learning Test II (CVLT-II), revised Brief Visuospatial retention Test (BVRT-R) of BICAMS-A and serum BDNF in both study and control groups. There was a significant increase in CVLT-II, BVRT-R of BICAMS-A and serum BDNF in the study group compared to the control group (P < 0.05)., Conclusion: Vestibular training is an effective and innovative approach for improving cognitive functions in PwMS., Trial Registration: PACTR202311670782148., Competing Interests: Declaration of competing interest No conflict of interest existed., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Executive dysfunction and dysregulated inflammation are found in patients with different psychiatric disorders. However, whether there are different associations between inflammatory markers and executive performance in patients with different psychiatric diagnoses is unknown. Our study aims were (1) to compare peripheral cytokine expression and executive function in patients with bipolar disorder (BD), substance use disorder (SUD), and schizophrenia (SCZ), and in healthy controls (HC) and (2) to explore the potential association between inflammatory cytokines and executive function in different patient groups and HC. Participants with BD (n = 816), SUD (opioid use disorder and/or methamphetamine use disorder, n = 518), SCZ (n = 146), and HC (n = 186) were recruited. Plasma cytokine levels [tumor necrosis factor (TNF)-α, interleukin (IL)-8 (only measured in 8 SCZ patients), transforming growth factor (TGF)-β1 (not measured in SCZ patients)], C-reactive protein (CRP), brain-derived neurotrophic factor (BDNF) levels, and executive function [Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT)] were assessed. We found that all patient groups had worse executive performance and higher inflammatory cytokine levels than the HC group. SCZ patients had the worst executive performance, while SUD patients had the highest inflammatory cytokine levels. Increased plasma IL-8, CRP, and TNF-α levels were specifically associated with worse executive function in BD, SUD, and SCZ patients (P = 0.009, 0.04, and 0.03, respectively). We concluded that dysregulated inflammation might be a transdiagnostic feature among different psychiatric disorders and associated with executive dysfunction. Further studies to investigate the causal relationship and mechanisms between inflammation and executive dysfunction may be needed., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: This systematic review and meta-analysis evaluates peripheral and CNS BDNF levels in glioma patients., Methods: Following PRISMA guidelines, we systematically searched databases for studies measuring BDNF in glioma patients and controls. After screening and data extraction, we conducted quality assessment, meta-analysis, and meta-regression., Results: Eight studies were included. Meta-analysis showed significantly reduced plasma BDNF levels in glioma patients versus controls (SMD: -1.0026; 95% CI: [-1.5284, -0.4769], p = 0.0002). High-grade gliomas had lower plasma BDNF (p = 0.0288). Tissue BDNF levels were higher in glioma patients (SMD: 1.9513; 95% CI: [0.7365, 3.1661], p = 0.0016) and correlated with tumor grade (p = 0.0122). Plasma BDNF levels negatively correlated with patient age (p = 0.0244) and positively with female percentage (p = 0.0007)., Conclusion: BDNF is a promising biomarker in glioma, showing significant changes in plasma and tissue levels correlating with tumor grade, patient age, and gender., (© 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

The prevalence of Alzheimer's disease (AD) is on the rise globally, and everyone who develops AD eventually experiences mild cognitive impairment (MCI) first. Timely intervention at an early stage of the disease may mitigate disease progression. Recent studies indicate that BDNF and MMP-9 play a significant role in the pathogenesis of AD. Therefore, this study aims to ascertain whether there are differences in plasma BDNF and MMP-9 levels between individuals with mild cognitive impairment due to AD and those with normal cognition, and to analyze the factors influencing mild cognitive impairment.This case-control study included 102 individuals with mild cognitive impairment and 102 controls, matched by age and sex. Participants completed a series of questionnaires, neuropsychological assessments, and clinical examinations. Plasma concentrations of BDNF and MMP-9 of the participants were quantified using ELISA. Subsequently, the factors influencing MCI were analyzed using univariate and multivariate logistic regression. The differences in plasma BDNF levels, MOCA total scores, and scores in various cognitive domains (including visuospatial and executive abilities, abstract thinking, attention, language, naming, and delayed memory) between the MCI and the control groups showed statistically significant (p < 0.05). Logistic regression analysis revealed that plasma BDNF levels and years of formal education were significantly negatively associated with MCI. This study indicates that plasma BDNF and years of formal education are protective factors influencing cognitive function., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the ethics committees of Shihezi People’s Hospital under the Declaration of Helsinki (KJ-2023-06). All participants included in the study were informed about the aims and methods of the study and provided their written informed consent. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Sulfur mustard (SM), a chemical warfare weapon has been used in conflicts. The delayed impact of sulfur mustard on mental and physical health of veterans remains a topic of significant concern. This cross-sectional study investigated the serum levels of brain-derived neurotrophic factor (BDNF), interleukin (IL)-1β, and IL-6 in 227 SM-chemical veterans receiving long-term financial support and 77 healthy individuals. Their mental health status and life satisfaction were assessed through three self-report questionnaires (General Health Questionnaire - 28, GHQ-28; Depression, Anxiety & Stress Scale, DASS-21; 36-Item Short Form Survey, SF-36). Our findings revealed higher levels of anxiety/insomnia, and psychiatric symptoms in the veterans compared to the control group (P < 0.05), accompanied by depression, stress, and anxiety as measured by the GHQ-28 and DASS-21 assessments. Severe depression and social dysfunction were not prevalent in the veterans compared to the control group (P > 0.05) according to the GHQ-28 findings. The SF-36 assessment indicated overall better health conditions for SM participants, with higher scores across various domains (general health, social function, and mental health) and two mental and physical dimensions in the veterans compared to the control group (P < 0.05). IL-1β and IL-6 levels were lower in the SM-exposed group than in the control group, while the BDNF level was higher in the SM-exposed group (P < 0.05). Alterations in BDNF, IL-1β, and IL-6 levels along with results of the mentioned questionnaires may be evidence of partial improvement in the mental and physical health of the SM-exposed individuals receiving the financial support., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Backgrounds: This study aimed to examine the individual and combined effects of serum BDNF (sBDNF) levels and alcohol consumption status, assessed shortly after a physical injury, on the development of post-traumatic stress disorder (PTSD) over two years., Methods: Participants were consecutively recruited from a trauma center and followed prospectively for two years. At baseline, sBDNF levels and alcohol consumption history were assessed. A range of socio-demographic and clinical covariates were also collected. PTSD diagnosis during follow-up (3, 6, 12, and 24 months post-injury) was established using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were employed to investigate the relationships between sBDNF levels, alcohol consumption status, and PTSD onset., Results: Out of 923 participants analyzed, 112 (12.1%) developed PTSD at some point during the study, with prevalence rates of 8.8% at 3 months, 7.6% at 6 months, 4.8% at 12 months, and 3.7% at 24 months. The study found no individual associations between sBDNF levels or alcohol consumption status and PTSD development. However, lower sBDNF levels significantly predicted PTSD in individuals who consumed alcohol, a relationship not observed in non-drinkers, with significant interaction terms. This pattern was consistent at later follow-up points from 12 to 24 months, but not at earlier assessments at 3 and 6 months., Limitations: The study's reliance on participants from a single trauma center with moderate to severe injuries may limit the generalizability of the findings., Conclusions: A significant interaction between sBDNF levels and alcohol consumption in relation to PTSD development was observed, particularly in the long term. These findings highlight the necessity of considering both sBDNF levels and alcohol consumption in strategies aimed at preventing PTSD among individuals with physical injuries, underscoring the need for tailored approaches based on these factors., Competing Interests: Declaration of competing interest No potential conflict of interest relevant to this article was reported., (Copyright © 2024. Published by Elsevier Inc.)

Background/Objectives: Although physical activity and balanced diet may increase peripheral brain-derived neurotrophic factor (BDNF) concentration, little is known about whether these factors modify BDNF content in physically active individuals and whether the serum fatty acid (FA) profile is related. This study aimed to evaluate quality of diet, identify specific dietary patterns and assess their influence on BDNF and FA levels in serum. It is hypothesized that there is a correlation between diet quality and the concentrations of BDNF and FA in the serum of physically active male individuals. Methods: Physically active young adult male students at Jozef Pilsudski University of Physical Education in Warsaw (Poland) were enrolled. Dietary patterns were identified with cluster analysis and linear discriminant analysis (LDA) based on responses to a validated food frequency questionnaire, KomPAN ® version 1.1. Results : Consumption of beverages, vegetables, milk, wholemeal bread/rolls, fruit and vegetable juices, butter, tinned vegetables and fruits were significant in the LDA model, in which three clusters were distinguished. Cluster 1 was characterized by more frequent consumption of wholemeal bread/rolls, milk, fruits, vegetables, fruit and vegetable juices and sweetened hot beverages and by significantly greater values for the pro-healthy diet index ( p < 0.0001) and diet quality index ( p < 0.0001) compared to Clusters 2 and 3. The diet of Cluster 2 was of the worst quality, as indicated by the higher values of the not-healthy diet index. Cluster 1 had the tendency for the highest BDNF levels (of the best quality of diet), and a tendency for decreased BDNF concentration with an increased physical activity level was observed. Conclusions : Physical activity, diet quality and BDNF level depend, correlate and interact with each other to provide both optimal physical and mental health.

Aims: To evaluate the relation between maternal concentrations of progranulin (PGRN), adipocyte fatty acid-binding protein (AFABP), brain-derived neurotrophic factor (BDNF), and fibroblast growth factor 21 (FGF21) throughout pregnancy with neonatal weight and length at birth and at one month of age, as well as with the percentage of fat mass at one month of age. Besides, we evaluated the association between maternal organokine concentrations with pregestational nutritional status and gestational weight gain (GWG)., Methods: Longitudinal study of 100 healthy pregnant women and their neonates. Conventional biochemical tests were performed and maternal organokine concentrations were measured by ELISA. Neonatal percent fat mass was determined using the PEA POD system, and weight and length were measured using a soft tape measure and a baby scale. Multiple linear regression models were made to predict neonatal anthropometric measurements and adiposity., Results: In all women, PGRN concentrations significantly increased as pregnancy progressed, while AFABP concentrations increased until the third trimester and the highest BDNF concentrations were observed in the second trimester of pregnancy. In contrast, FGF21 concentrations did not change during pregnancy. Only maternal obesity was associated with some differences in AFABP and FGF21 concentrations. Gestational age at birth, maternal age and third-trimester PGRN concentrations predicted weight (gestational age at birth: β=0.11; maternal age: β=-0.033; PGRN: β=0.003, p <0.001) and, together with first-trimester BDNF concentrations, length (gestational age at birth: β=0.76; maternal age: β=-0.21; PGRN: β=0.24; BDNF: β=0.06, p <0.001) at birth. Maternal age and third-trimester BDNF concentrations predicted one-month-old neonate length (maternal age: β=-1.03; BDNF: β=0.45, p <0.001). Pregestational body mass index (pBMI), GWG, second-trimester FGF21 concentrations, and third-trimester AFABP concentrations predicted neonatal fat mass percentage (pBMI: β=-0.58; GWG: β=-0.32; FGF21: β=-0.004; AFABP: β=-1.27, p <0.001) at one month of age., Conclusion: Maternal PGRN, AFABP, and BDNF concentrations, but not FGF21, vary throughout pregnancy. These organokines and maternal characteristics can be useful in the prediction of neonatal weight, length, and percentage fat mass., Competing Interests: OP-P is a speaker of Nestle Nutrition Institute and Exeltis Pharma Mexico. No relationship of any kind exists regarding this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Valencia-Ortega, Galicia-Hernández, Castillo-Santos, Molerés-Orduña, Arceo-Cerna, Perichart-Perera, Rodríguez-Cano, Rodríguez-Hernández, Estrada-Gutierrez, Camacho-Arroyo and Solis-Paredes.)

Blast neurotrauma has been linked to impairments in higher-order cognitive functions, including memory, attention, and mood. Current literature is limited to a single overpressure exposure or repeated exposures at the same level of overpressure. In this study, a rodent model of primary blast neurotrauma was employed to determine the pressure at which acute and chronic neurological alterations occurred. Three pressure magnitudes (low, moderate and high) were used to evaluate injury thresholds. A biology shock tube (BST) was used to simulate shock waves with overpressures of 60 kPa, 90 kPa and 120 kPa respectively. Neurological behavior of the rats was assessed by the Multi-Conditioning System (MCS) at 1 d, 7 d, 28 d and 90 d after shock wave exposure. Serum dopamine (DA), 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF) and gamma-aminobutyric acid (GABA) were measured at the same time points. The proteomic analysis was conducted to identify potentially vulnerable cellular and molecule targets of serum in the immediate post-exposure period. Results revealed that: (1) Anxiety-like behavior increased significantly at 1 d post-exposure in the medium and high overpressure (90 kPa, 120 kPa) groups, returned to baseline at 7 days, and anxiety-like behavior in the high overpressure groups re-emerged at 28 d and 90 d. (2) High overpressure (120 kPa) impaired learning and memory in the immediate post-exposure period. (3) The serum DA levels decreased significantly at 1 d post-exposure in the medium and high overpressure groups; The 5-HT levels decreased significantly at 1 d and 90 d in the high overpressure groups; The BDNF levels decreased significantly at 90 d in the high overpressure groups. (4) Proteomic analysis identified 38, 306, and 57 differentially expressed proteins in serum following low, medium and high overpressure exposures, respectively. Two co-expressed proteins were validated. Functional analysis revealed significant enrichment of 1121, 2096, and 1121 Gene Ontology (GO) items and 33, 47, and 26 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, indicating extensive molecular responses to overpressure in the early phase. These findings suggest that exposure, even at moderate levels, can induce persistent neurobehavioral and molecular alterations, highlighting the need for further research into the long-term consequences of blast neurotrauma., Competing Interests: Declarations. Competing interests: We have no conflicts of interest to declare. Ethics approval: All methods were carried out in accordance with relevant guidelines and regulations. The protocols for all animal experiments were approved by the Animal Welfare Committee of Institute for Hygiene of Ordnance Industry, China. Ethical Statement: This study and included experimental procedures were approved by the institutional animal care and use committee of institute for hygiene of ordnance industry (approval no. IACUC202302). The study is reported in accordance with ARRIVE guidelines. All animal housing and experiments were conducted in strict accordance with the institutional guidelines for care and use of laboratory animals., (© 2024. The Author(s).)

Aim: Therapeutic latency, lack of response, and adverse drug reactions are major challenges in current treatment approaches for major depressive disorder (MDD). Following the success of ketamine, more clinical research on NMDA antagonists is needed for a safe and long-term therapy in MDD. Hence, this study was conducted to evaluate the efficacy and safety of adjunct dextromethorphan to SSRIs in MDD., Methods: In this randomized, double-blind, add-on, placebo-controlled, group sequential design clinical trial, 60 patients with MDD were randomized to receive either adjunct dextromethorphan (30 mg) or adjunct placebo to SSRI for eight weeks. The primary outcome was the change in the MADRS score over eight weeks, and the secondary outcome parameters were response rate, remission rate, change in CGI-S, CGI-I, change in serum BDNF and serum dextromethorphan., Results: The results showed a significantly greater reduction in MADRS score from baseline (MD: -3.94; 95 %CI: -5.81 to -2.06; p < 0.001; Cohen's d: 1.05), reduction in CGI-S score (p = 0.002), higher response (p = 0.008) and remission (p = 0.007) rate in the test group compared to the control group. The test group also showed significantly better CGI-I score (p = 0.001) compared to the control group. However, no significant difference was found in the change in serum BDNF (p = 0.751) between the groups. In the test group, serum dextromethorphan levels in all patients were within the therapeutic range. The occurrence of adverse events was comparable in both study groups., Conclusion: Early augmentation of SSRIs with dextromethorphan (30 mg/day) for the treatment of mild to moderate MDD may improve clinical outcomes significantly in terms of improvement in symptoms, response rate and remission rate. Trial registration ClinicalTrials.gov identifier: NCT05181527., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Transcranial direct current stimulation (tDCS) and foot drop stimulators (FDS) are widely used for stroke rehabilitation. However, no study has investigated if tDCS could boost the effects of FDS and gait training in improving clinical parameters and neuroplasticity biomarkers of chronic post-stroke subjects., Objective: To investigate the effects of combining tDCS and FDS on motor impairment, functional mobility, and brain-derived neurotrophic factor (BDNF) serum levels. Also, to evaluate the effects of this protocol on the insulin-like growth factor-1 (IGF-1), insulin growth factor-binding proteins-3 (IGFBP-3), interleukin (IL) 6 and 10, and tumor necrosis factor-α (TNF-α) levels., Methods: Thirty-two chronic post-stroke individuals were randomized to tDCS plus FDS or sham tDCS plus FDS groups. Both groups underwent ten gait training sessions for two weeks using a FDS device and real or sham tDCS. Blood samples and clinical data were acquired before and after the intervention. Motor impairment was assessed by the Fugl-Meyer Assessment and functional mobility using the Timed up and Go test., Results: Both groups improved the motor impairment and functional mobility and increased the BDNF levels. Both groups also increased the IL-10 and decreased the cortisol, IL-6, and TNF-α levels. No difference was observed between groups., Conclusion: tDCS did not add effect to FDS and gait training in improving clinical parameters and neuroplasticity biomarkers in chronic post-stroke individuals. Only FDS and gait training might be enough for people with chronic stroke to modify some clinical parameters and neuroplasticity biomarkers.

Background: Animal and human studies have shown that exposure to hypoxia can increase brain-derived neurotrophic factor (BDNF) protein transcription and reduce systematic inflammatory cytokine response. Therefore, the aim of this study was to investigate the acute and chronic effects of intermittent hypoxic-hyperoxic exposure (IHHE) prior to aerobic exercise on BDNF, interleukin-6 (IL-6), and C-reactive protein (CRP) blood levels in geriatric patients., Patients and Methods: Twenty-five geriatric patients (83.1 ± 5.0 yrs, 71.1 ± 10.0 kg, 1.8 ± 0.9 m) participated in a placebo-controlled, single-blinded trial and were randomly assigned to either an intervention (IG) or control group (CG) performing an aerobic cycling training (17 sessions, 20 min·session -1 , 3 sessions·week -1 ). Prior to aerobic cycling exercise, the IG was additionally exposed to IHHE for 30 min, whereas the CG received continuous normoxic air. Blood samples were taken immediately before (pre-exercise) and 10 min (post-exercise) after the first session as well as 48 h (post-training) after the last session to determine serum (BDNF S ) and plasma BDNF (BDNF P ), IL-6, and CRP levels. Intervention effects were analyzed using a 2 x 2 analysis of covariance with repeated measures. Results were interpreted based on effect sizes with a medium effect considered as meaningful (η p 2 ≥ 0.06, d  ≥ 0.5)., Results: CRP was moderately higher ( d  = 0.51) in the CG compared to the IG at baseline. IHHE had no acute effect on BDNF S (η p 2 = 0.01), BDNF P (η p 2 < 0.01), BDNF serum/plasma-ratio (η p 2 < 0.01), IL-6 (η p 2 < 0.01), or CRP (η p 2 = 0.04). After the 6-week intervention, an interaction was found for BDNF serum/plasma-ratio (η p 2 = 0.06) but not for BDNF S (η p 2 = 0.04), BDNF P (η p 2 < 0.01), IL-6 (η p 2 < 0.01), or CRP (η p 2 < 0.01). BDNF serum/plasma-ratio increased from pre-exercise to post-training ( d  = 0.67) in the CG compared to the IG ( d  = 0.51). A main effect of time was found for BDNF P (η p 2 = 0.09) but not for BDNF S (η p 2 = 0.02). Within-group post-hoc analyses revealed a training-related reduction in BDNF P in the IG and CG by 46.1% ( d  = 0.73) and 24.7% ( d  = 0.57), respectively., Conclusion: The addition of 30 min IHHE prior to 20 min aerobic cycling seems not to be effective to increase BDNF S and BDNF P or to reduce IL-6 and CRP levels in geriatric patients after a 6-week intervention.The study was retrospectively registered at drks.de (DRKS-ID: DRKS00025130).

Background: Cognitive impairment is a core feature of schizophrenia with unclear mechanisms, particularly neurocognition. The objective of this study was to investigate the association between duration of untreated psychosis (DUP) and neurocognition, as well as potential biological mechanisms., Methods: A total of 219 patients were recruited in this study. DUP was measured in years, reflecting the untreated period. Neurocognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). The plasma concentrations of three growth factors, vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and epidermal Growth Factor (EGF) were detected by enzyme-linked immunosorbent assay in 128 patients. Multiple linear regression analysis was used to analyze the association between DUP, growth factors, and neurocognition., Results: Our findings showed that DUP was significantly negatively correlated with speed of processing and reasoning and problem-solving in all patients (N = 219, P < 0.05). Five years was defined as cut-off point for long and short DUP group in the present study. Only in the short DUP patients, DUP was strongly associated with visual learning and neurocognition (P < 0.05). In patients with growth factor (N = 128), DUP was independently associated with speed of processing, verbal learning, and neurocognition (P < 0.05). Further, plasma concentrations of VEGF, BDNF, and EGF were all significantly correlated with neurocognition (P < 0.05). Additionally, we found a potential trend of correlation between DUP and BDNF (P = 0.061)., Conclusion: Our study provides insights into a negative correlation between DUP and neurocognition, and BDNF may serve as a potential biological mechanism., Competing Interests: Declaration of competing interest The authors have no conflict of interest to report., (Copyright © 2024. Published by Elsevier B.V.)

This longitudinal study explored the intricate relationships between serum Brain-Derived Neurotrophic Factor (sBDNF) levels, exposure to childhood adversities, and the subsequent development of Post-Traumatic Stress Disorder (PTSD), distinguishing between earlier- and delayed-onset forms over a two-year follow-up period in individuals sustaining physical injuries. We recruited patients presenting with moderate to severe physical injuries at a trauma center, conducting baseline assessments of sBDNF levels and childhood adversities through the Adverse Childhood Experiences (ACE) questionnaire. Additionally, detailed socio-demographic and clinical data were compiled. The Clinician-Administered PTSD Scale for DSM-5 was employed to diagnose PTSD at 3, 6, 12, and 24 months post-injury. Binary and multinomial logistic regression analyses were applied to elucidate the interactions between sBDNF levels, childhood adversities, and PTSD onset patterns. Among 895 participants, PTSD was diagnosed in 107 individuals (11.9 %), with 76 (8.4 %) exhibiting symptoms indicative of earlier-onset PTSD and 31 (3.5 %) demonstrating delayed-onset PTSD. Significantly, lower sBDNF levels were associated with a higher risk of earlier-onset PTSD specifically in the context of childhood adversities. This association was not observed in individuals without childhood adversities or in those with delayed-onset PTSD. The findings suggest a complex and critical interplay between neurobiological factors, specifically sBDNF levels, and early life adversities in influencing the timing of PTSD onset, potentially deepening the understanding of PTSD etiology., Competing Interests: Declaration of Competing Interest No potential conflict of interest relevant to this article was reported., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The neurotrophic protein brain-derived neurotrophic factor (BDNF) plays a pivotal role in brain function and is affected by acute and chronic stress. We here investigate the patterns of BDNF and cortisol stress reactivity and recovery under the standardized stress protocol of the TSST and the effect of perceived chronic stress on the basal BDNF levels in healthy young men. Twenty-nine lean young men underwent the Trier Social Stress Test (TSST) and a resting condition. Serum BDNF and cortisol were measured before and repeatedly after both conditions. The perception of chronic stress was assessed by the Trier Inventory for Chronic Stress (TICS). After the TSST, there was a significant increase over time for BDNF and cortisol. Stronger increase in cortisol in response to stress was linked to an accelerated BDNF decline after stress. Basal resting levels of BDNF was significantly predicted by chronic stress perception. The increased BDNF level following psychosocial stress suggest a stress-induced neuroprotective mechanism. The presumed interplay between BDNF and the HPA-axis indicates an antagonistic relationship of cortisol on BDNF recovery post-stress. Chronically elevated high cortisol levels, as present in chronic stress, could thereby contribute to reduced neurogenesis, and an increased risk of neurodegenerative conditions in persons suffering from chronic stress., Competing Interests: Declaration of Competing Interest The authors certify that they have NO conflict of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chronic Non-Communicable Diseases (NCDs), including cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes, are the leading global causes of mortality, accounting for 71 % of deaths annually. Metabolic Syndrome (MS), characterized by hypertension, obesity, insulin resistance, and dyslipidemia, is a significant risk factor for NCDs. Physical inactivity exacerbates these conditions, contributing to poor cardiovascular and mental health outcomes., Objective: To analyze the effects of physical exercise on Irisin and Brain-Derived Neurotrophic Factor (BDNF) concentrations and their relationship with cardiometabolic and mental health of individuals with MS., Methods: A systematic review was conducted of articles published between August 2023 and June 2024 in ScienceDirect, PubMed, and SciELO, following PRISMA guidelines. Inclusion criteria encompassed observational studies, clinical trials, and reviews with high methodological quality. The review focused on Irisin, BDNF, physical exercise, and MS., Results: A total of 584 articles were identified, with 43 selected for detailed analysis. The review highlights that physical exercise significantly impacts Irisin and BDNF levels, which in turn influence metabolic and mental health. Irisin, a myokine secreted during exercise, promotes the conversion of white adipose tissue to brown adipose tissue, enhancing energy expenditure and metabolic health. Elevated Irisin levels are associated with improved cognitive function and mental well-being. BDNF, a neurotrophin, supports neuronal growth and cognitive function. Exercise-induced increases in BDNF levels are linked to enhanced neuroplasticity, reduced anxiety, and improved mood., Conclusion: Understanding the role of Irisin and BDNF in response to physical exercise offers valuable insights for developing strategies to manage and prevent MS and its related mental health issues. Further research is needed to elucidate the molecular mechanisms involved., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Luisa Moscoso-Loaiza reports article publishing charges was provided by National University of Colombia. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Brain-derived neurotrophic factor (BDNF) is a protein important for synaptic plasticity and formation of memory. It is suggested to play an important role in the development of psychiatric disorders like post-traumatic stress disorder (PTSD). Individuals with PTSD usually show decreased BDNF levels in serum. Physical exercise has shown to be effective in increasing serum BDNF levels., Objective: As the most beneficial form of exercise to raise serum BDNF levels in individuals with PTSD is yet to be determined, we compared two training protocols and their effects on BDNF release. We expected that a training with higher intensity increases BDNF serum levels more than a low intensity training (LIT)., Method: 40 participants (80% female) diagnosed with PTSD were randomized to either high-intensity interval training (HIIT) or a low intensity training group (LIT). They underwent a 12-day training period. We measured serum BDNF levels pre- and post-exercise on first and last intervention day. BDNF was controlled for platelet counts., Results: In the HIIT group there was a significant increase in serum BDNF post-exercise on both days measured, respectively when controlled for platelets. The increase was transient. Both groups did not show an increase in serum BDNF over the course of the 12-day training period., Conclusion: A single session of HIIT raised serum BDNF levels in individuals with PTSD transiently. Neither HIIT nor LIT raised serum BDNF levels over the course of 12 days., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Infections of the nervous system, such as acute bacterial meningitis, pose serious health problems that require immediate intervention. In experimental animals, exposure to lipopolysaccharide (LPS) is used to induce meningitis. Aside from drug intervention to reduce inflammation in meningitis, aerobic exercise helps to maintain the regulatory mechanisms of brain homeostasis through anti-inflammatory mechanisms. The aim of this study was to evaluate the effect of aerobic exercise on malondialdehyde (MDA), nuclear factor-kappa B (NF-κB), insulin-like growth factor 1 (IGF-1), endothelial nitric oxide synthase (eNOS), brain-derived neurotrophic factor (BDNF), apoptosis, and spatial memory. A four-week experimental study was conducted using 18 rats, which were randomly divided into three different groups (six rats per group): healthy rats as negative controls (non-meningitis), a treatment group treated with antibiotic treatment (meningitis group), and a third group (aerobic exercise group) treated with antibiotics and aerobic exercise following LPS-induced meningitis. Data were analyzed using a one-way analysis of variance (ANOVA) test, and the comparison between groups used the Bonferroni post-hoc test. The results showed that aerobic exercise significantly reduced MDA ( p <0.001), NF-κB ( p =0.035), and apoptosis ( p =0.020) while increasing the serum levels of IGF-1 ( p <0.001), eNOS ( p =0.011), and BDNF ( p =0.001) levels. Improvement in spatial memory was significant in the aerobic exercise group ( p <0.001). This study suggested that aerobic exercise could be a promising adjunct therapy in meningitis management strategies, particularly due to its effect on improving spatial memory. Further clinical trials are needed to confirm these findings for clinical use., Competing Interests: All the authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Background: Per- and polyfluoroalkyl substances (PFAS) is perceived as an emerging environmental endocrine disruptor, which have been linked to children neurodevelopment. However, the potential mechanisms are not clear. Brain-derived neurotrophic factor (BDNF) is a vital protein in neurodevelopment, and the associations between PFAS exposure and BDNF require exploration., Objective: We aimed to explore the relationships between PFAS exposure and the levels of BDNF in cord serum., Methods: A total of 1,189 mother-infant dyads from the Sheyang Mini Birth Cohort Study (SMBCS) were enrolled. The levels of 12 PFAS and BDNF were measured in cord serum. We utilized generalized linear models (GLMs), quantile-based g-computation (QGC) models, and Bayesian Kernel Machine Regression (BKMR) models to explore the relationships between single and mixed PFAS exposure and BDNF concentration. Additionally, the potential sex differences were explored by sex-stratified analysis., Results: Median concentrations of the included 10 PFAS ranged from 0.04 to 3.97 μg/L. In the single chemical models, four PFAS congeners, namely perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), were negatively associated with BDNF levels in cord serum among females only (β: -0.116 to -0.062, p < 0.05). In the BKMR models of total mother-infant dyads and female fetuses, the significant negative relationships between PFAS mixtures and BDNF were observed, and PFUnDA was identified as an important contributor (Posterior inclusion probability, PIP = 0.8584 for the total subjects; PIP = 0.8488 for the females). PFOS was another important driver based on the mixture approaches., Conclusions: We found that PFNA, PFOS, PFDA, and PFUnDA were associated with decreased BDNF concentration in the females, although the causal inference might be limited. PFAS mixtures were also negatively linked with BDNF levels in the total mother-infant pairs and female fetuses. The adverse effect of PFAS exposure on fetal BDNF levels might be sex-specific., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Zhijun Zhou reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Evaluation of the biomarkers and their relations with sleep in attention deficit hyperactivity disorder (ADHD) is important for understanding the impairments in cognitive functioning. In this study, we aimed to investigate the brain-derived neurotrophic factor (BDNF) and sialic acid (Sia) levels, and their possible relations with chronotypes in ADHD., Methods: The study included 100 drug-naive children with ADHD and 74 healthy children as controls. Conners' Parent Rating Scale-Revised (CPRS-R) scores were used for the severity assessment. Morningness Eveningness Questionnaire (MEQ) was used to determine the chronotypes of participants. ELISA kits were used for the assessment of BDNF and Sia plasma levels., Results: Levels of BDNF and Sia were found to be statistically significantly higher in the ADHD group compared to healthy children (p < 0.001, p < 0.001, respectively). BDNF and Sia levels were found to be higher in the ADHD group with eveningness chronotype (p = 0.045, p = 0.038). The binary logistic regression model was statistically significant (p = 0.033), higher BDNF and Sia levels were assessed as predictive factors for the diagnosis of ADHD. Also, eveningness chronotype was found as a predictive factor of BDNF and Sia levels in ADHD., Conclusion: The results indicate that BDNF and Sia levels, which are related to cognitive functions and sleep, increase with the age of ADHD. Eveningness chronotype, connected with the severity of ADHD, is related to BDNF and Sia levels. There is a need for further studies to confirm these results., (© 2024 International Society for Developmental Neuroscience.)

Objectives: To investigate the effects of transcranial direct current stimulation (tDCS) on brain-derived neurotrophic factor (BDNF) levels, craving, and executive functions in individuals on maintenance treatment for opioid use., Methods: We randomized 70 right-handed men aged 18-55 years into 2 groups: the intervention group and the sham group. The intervention was 10 sessions of 2 mA stimulation over 5 days. Each session in the sham group ended after 30 seconds. Craving was measured using the Desire for Drug Questionnaire (DDQ), Obsessive Compulsive Drug Use Scale (OCDUS), and visual analog scale (VAS). The measurements were taken before and after the intervention, as well as 2 months later. BDNF was measured before and after the intervention. Repeated-measures analysis of variance, the generalized estimating equation model, and independent t test were used for data analysis., Results: The mean differences (95% confidence intervals) in pre and post craving scores in the intervention group were (12.71 [9.10 to 16.32], P = 0.167) for VAS, (1.54 [1.12 to 1.96], P = 0.012) for OCDUS, and (1.71 [1.27 to 2.15], P = 0.125) for DDQ. These measures in the control group were -0.44 (-1.19 to 0.30), 0.01 (-0.21 to 0.23), and 0.126 (-0.11 to 0.36), respectively. BDNF serum levels significantly increased after the intervention (difference, 0.84 [0.69 to 0.99], P < 0.001); however, this change was not significant in the generalized estimating equation model. The effect of tDCS on craving was significant in OCDUS, but not significant in VAS and DDQ., Conclusions: The tDCS reduces craving and improves executive functions in the short term. BDNF serum level was not associated with tDCS., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Cognitive impairment occurs throughout the entire course of and affects the work and life of patients with major depressive disorder (MDD). The gut microbiota, kynurenine pathway (KP) and inflammatory response may have important roles in the mechanism of cognitive impairment in MDD patients. Consequently, our goal was to investigate the association among the gut microbiota, inflammation, KP, and cognition in MDD., Method: We enrolled patients with MDD (N = 86) and healthy controls (HCs, N = 120) in this research. The study involved participant data regarding the levels of serum inflammatory factors (interleukin [IL]-1β, IL-4, IL-6, brain-derived neurotropic factor [BNDF], migration inhibitory factor [MIF], tumor necrosis factor [TNF]-α, vascular endothelial growth factor [VEGF]), gut microbiota and cognitive function (MCCB) were collected., Results: Patients demonstrated poorer cognitive function. Gut microbiota, such as Bacteroide, Prevotella, Faecalibacterium and Parabacteroides between MDDs and HCs were significantly different. Moreover, in patients with MDD, we found that different microbiomes were related to cognition and that Acidaminococcus was positively correlated with multiple domains of cognition. Allisonella and Acidaminococcus were significantly positively correlated with BDNF and negatively correlated with MIF. Alloprevotella, Blautia, and Megamonas were positively correlated with kynurenine/tryptophan (KYN/TRP). Acidaminococcus was negatively correlated with 3-hydroxykynurenine (3-HK). BDNF levels was significantly positive correlated with kynurenic acid (KA) and quinolinic acid (QA)., Conclusion: The results of the present study suggest that the gut microbiota is associated with cognitive function, cytokine levels and KP metabolism in patients with MDD; however, the mechanism of the interaction between cognition and gut microbiota in MDD patients require further investigation., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Multiple sclerosis (MS) is a chronic neurological disorder characterized by demyelination and neurodegeneration, leading to various physical, cognitive, and emotional challenges. Dual-task (DT) training, involving performing mental and physical tasks simultaneously, addresses the complex interaction between motor and cognitive functions., Purpose: Given the extensive physical, cognitive, and mood-related issues in this population, this study aimed to examine the effects of combined aerobic-cognitive training (Brythonic) and aerobic training on brain-derived neurotrophic factor (BDNF), DT performance, and mood state in MS patients., Methods: Thirty patients (22 women and 8 men) with relapsing-remitting multiple sclerosis (RRMS) and an expanded disability status scale (EDSS) score below four were randomly assigned to three groups: aerobic-cognitive training (Brythonic), aerobic training, and control. The training groups participated in 10 weeks of home-based online training, with two sessions per week. Each session included a 10-minute warmup, 15 to 35 min of exercise, and a 5-minute cool-down. The Brythonic group performed aerobic movements while reciting motivational words, forming a complete positive sentence over ten weeks. The aerobic group performed the same movements without cognitive tasks. Serum BDNF levels, DT performance, and profile of mood states (POMS) were measured before and after the 10-week training period. A two-way ANOVA with repeated measures was used to analyze differences between and within groups, with a significance level of P ≤ 0.05., Results: BDNF levels significantly increased in the Brythonic group (P = 0.048) and significantly decreased in the control group compared to baseline. In the DT test, the Brythonic group showed significant improvements in the number of correct answers and DT values compared to the aerobic and control groups. The Brythonic group also had a significantly reduced response time compared to the control group. Additionally, selective speed significantly increased in both training groups. In the POMS test, the Brythonic group showed significant improvements in all items except depression compared to the control group. Within the Brythonic group, all items significantly improved from baseline., Conclusion: This study demonstrated that combining motivational words with aerobic movements significantly impacts BDNF levels, DT performance, and mood states. Adding mental exertion to physical activity appears beneficial for patients with MS. Future studies should re-examine these findings with a larger patient cohort., Competing Interests: Declaration of conflicting interests None., (Copyright © 2024. Published by Elsevier Inc.)

Low-extremity ischemic disease is a common complication in diabetic patients, leading to reduced quality of life and potential amputation. This study investigated the therapeutic effect of spinal cord stimulation (SCS) on patients with diabetic foot disease and a rat model of diabetic foot injury. SCS was applied to patients with diabetic foot disease, with clinical assessments performed before and after therapy. Blood levels of NGF, BDNF, and NT-3 were determined by ELISA. A rat model of diabetic foot injury was established to validate NT-3's role in SCS therapy. SCS therapy improved the condition of patients with diabetic ischemic foot disease and promoted wound healing in the rat model. NT-3 levels significantly increased after SCS therapy in both patients and rats. Recombinant NT-3 administration improved wound healing and re-vascularization in the rat model, while NT-3 neutralization abrogated SCS's therapeutic effect. SCS improves the condition of patients with diabetic ischemic foot disease by inducing NT-3 production. Both SCS and NT-3 supplementation show therapeutic potential for ameliorating diabetic foot disease., Competing Interests: Declarations. Conflict of interest: The authors of this study promise to be free of any conflicts of interest. Ethical approval and consent to participate: All animal experiments involved in this study have been permitted and approved., (© 2024. The Author(s).)

Objectives: To investigate the repair effects of He's qiangtong method of acupuncture (involved bloodletting technique with strong action of unblocking) on the neurovascular unit of the patients with acute ischemic stroke (AIS) in terms of serological indicators so as to provide new ideas for the treatment of AIS., Methods: Seventy subjects with AIS were randomly divided into an observation group (35 cases, 1 case dropped out) and a control group (35 cases , 4 cases dropped out). Patients in the control group were treated with conventional regimen. In the observation group, the bloodletting was operated, combined with the conventional treatment. Bloodletting was performed at Baihui (GV20), Sishencong (EX-HN1) and bilateral Erjian (EX-HN6), using He's qiangtong method of acupuncture, 3 times a week and for 2 weeks. Before and after treatment, the scores of the national institute of health stroke scale (NIHSS), the modified Rankin scale (MRS), and the Barthel index were evaluated；and the serological levels of the serum brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and blood-brain barrier permeability-associated protein (S100β protein) were detected in the two groups., Results: After treatment, NIHSS score and MRS score were decreased ( P <0.01), and Barthel score was increased ( P <0.01) in both groups. NIHSS score of the observation group was lower than that of the control group ( P <0.01). Compared with those before treatment, the content of BDNF in both groups increased ( P <0.05), and VEGF content was elevated in the observation group ( P <0.05) after treatment. The total effective rate was 100% (34/34) in the observation group, higher than that (67.74%, 21/31) in the control group ( P <0.01)., Conclusions: He's qiangtong method of acupuncture can promote the recovery of neurological deficits in AIS patients and effectively improve their motor function and the activity of daily living, which may be related to the reconstruction of neurovascular unit in the brain of AIS patients by increasing the levels of serological repair factors.

Introduction: While numerous studies have established associations between brain-derived neurotrophic factor (BDNF) and cognitive functioning, limited research has delved into the role of BDNF concerning cognitive outcomes in atherosclerosis-related conditions. This study aimed to investigate the correlations between cognitive performance, serum BDNF levels, and the BDNF Val66Met polymorphism in individuals diagnosed with chronic limb ischemia (CLI)., Participants and Procedure: The study encompassed 159 CLI patients (52 females, 107 males) aged 59-73 years. Genetic analysis involved assessing the BDNF Val66Met single-nucleotide polymorphism using a TaqMan SNP Genotyping Assay and the ViiA™ 7 Real-Time PCR System. Serum BDNF levels were quantified. Cognitive functioning was evaluated through a computerized battery of tests, including the simple reaction test (SRT) for speed and accuracy assessment, verbal memory test (VMT) for short and long-term memory evaluation, and the GoNoGo test for cognitive control and inhibition., Results: Gender differences in cognitive performance were observed, with women excelling in VMT, while men demonstrated superior performance in SRT and the GoNoGo test. No statistically significant differences were noted between the Met/Met or Met/Val and Val/Val subgroups. However, notable differences emerged in female Met carriers, exhibiting superior VMT scores but more incorrect Go responses in the GoNoGo test. Conversely, female Val homozygotes showed significantly more incorrect NoGo responses compared to male Val homozygotes. In men carrying the Met allele, higher BDNF concentrations correlated with improved GoNoGo test results (r = 0.248, p = 0.01). Conversely, in women with the Val/Val variant, lower BDNF concentrations were associated with better VMT scores., Conclusions: This study underscores the sex-specific impact of BDNF serum levels and the BDNF polymorphism on cognitive processes among CLI patients. The findings highlight the nuanced influence of BDNF in shaping cognitive functioning, emphasizing the need for further research into these sex-dependent associations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chyrek-Tomaszewska, Popiołek, Stachowicz-Karpińska, Budzyński, Linkowska, Kozakiewicz, Szelągowski, Borkowska and Bieliński.)

Background: Bipolar disorder (BD) is hypothesized to be associated with accelerated biological aging. Telomere length (TL) is a biomarker of aging, and although TL decreases with each cell division, the rate of telomere shortening may be affected by inflammation. We aimed to investigate whether TL is decreased in BD patients and to determine the association between TL and inflammatory markers in such patients., Methods: 137 BD patients and 118 healthy controls (HCs) were recruited. Leukocyte TL and plasma levels of cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-8, IL-6, IL-10, transforming growth factor (TGF)-β1], C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were assessed., Results: TL did not differ significantly between the BD patients and HCs after adjustment for potential confounding factors (P = 0.79). TL was significantly negatively associated with age (β = -0.007, P < 0.001). In addition, log TNF-α levels were significantly negatively associated with TL (P = 0.009), in both the BD patients (P = 0.02) and HCs (P = 0.05)., Conclusion: We found a significant association between TNF-α levels and TL shortening in both BD patients and HCs. However, BD patients did not display increased TL shortening relative to HCs. Studies that involve larger sample sizes and control for the heterogeneity of BD participants will be needed., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Maintaining healthy brain function during ageing is of great importance, especially for the self-sufficiency of older adults. The main aim of this study was to determine the effects of dance and martial arts on exerkines Brain Derived Neurotrophic Factor (BDNF) and irisin blood serum levels., Methods: This randomized controlled trial examined the effects of dance and martial arts on serum Brain-Derived Neurotrophic Factor (BDNF) and irisin levels, as well as cognitive function, mood, and physical measures in older adults. Seventy-seven independently living older adults (mean age 70.3±3.8 years) were randomized into three groups: dance (DG), martial arts (MaG), and control (CG), followed over 12 weeks. Generalized linear models were used to assess the interventions' effects., Results: There was a significant increase in BDNF levels in both the DG (1.8 ± 4.9, p < 0.05) and MaG (3.5 ± 6.3, p < 0.05), while CG experienced a decrease (-4.9 ± 8.2, p < 0.05). Between-group effects were significant for BDNF, with DG and MaG showing higher levels than CG (p < 0.05). No significant changes in irisin levels were found. Cognitive performance, particularly attention and mental flexibility (measured by the Trail Making Test A and B), significantly improved in the DG compared to CG (p < 0.05). Additionally, participants in DG showed improved mood based on the Geriatric Depression Scale (p < 0.05) compared to CG. Anthropometric T-scores were significantly associated with changes in irisin levels (p < 0.05) after intervention., Conclusion: The study found that dance and martial arts upregulated BDNF levels, with dance showing notable improvements in cognitive function and mood in older adults. Changes in anthropometric measures were linked to increased irisin levels. These findings suggest that both dance and martial arts may promote healthy brain function in aging populations., Trial Registration: NCT05363228., Competing Interests: This manuscript has not been previously submitted or published and is not under consideration in any other peer-reviewed media. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Hola et al.)

It is debated whether CNS involvement begins during acute human immunodeficiency virus (HIV) infection in persons without meningitis/encephalitis and whether specific antiretroviral drugs or combinations would be beneficial. Neurologically asymptomatic participants enrolled in a randomized and controlled study comparing three combination antiretroviral regimens (tenofovir alafenamide/emtricitabine plus dolutegravir; darunavir; or both) during primary HIV infection were enrolled. Serum and CSF were collected at baseline and at 12 and 48 (serum only) weeks after treatment initiation. Single molecule array was used to measure neurofilament light chain (NFL), total tau protein (Tau), brain-derived neurotrophic factor, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase. We assessed the longitudinal change in biomarkers over time, in addition to the change in the prevalence of serum NFL concentrations above previously published age-adjusted cut-offs (7 pg/ml if 5-18 years, 10 pg/ml if 18-51 years, 15 pg/ml if 51-61 years, 20 pg/ml if 61-70 years and 35 pg/ml if >70 years). Serum was available from 47 participants at all time points, and CSF was available from 13 participants at baseline and 7 at Week 12. We observed a significant direct serum-to-CSF correlation for NFL (ρ = 0.692, P = 0.009), GFAP (ρ = 0.659, P = 0.014) and brain-derived neurotrophic factor (ρ = 0.587, P = 0.045). Serum (ρ = 0.560, P = 0.046) and CSF NFL (ρ = 0.582, P = 0.037) concentrations were directly associated with CSF HIV RNA levels. We observed a significant decrease over time in serum NFL (P = 0.006) and GFAP (P = 0.006) but not in the other biomarkers. No significant difference was observed among the treatment arms. At baseline, serum and CSF age-adjusted NFL levels were above age-adjusted cut-offs in 23 (48.9%) and four participants (30.8%), respectively; considering serum NFL, this proportion was lower at Weeks 12 (31.9%, P = 0.057) and 48 (27.7%, P = 0.13). A relevant proportion of neurologically asymptomatic participants had abnormal CSF and serum NFL levels during primary HIV infection. NFL and GFAP decreased in serum following combination antiretroviral therapy without significant differences among the treatment arms., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Increasing evidence demonstrates that brain-derived neurotrophic factor (BDNF) can be regarded as a biomarker for major depression. Our previous work found that the ratio of mature BDNF (mBDNF) to precursor-BDNF (proBDNF) was a pivotal factor in the pathogenesis of major depressive disorder (MDD). But the mechanism behind the ratio is still obscure. Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) both play essential roles in depression by regulating the ratio of BDNF/proBDNF. In present study, we analyzed BDNF, proBDNF, tPA and PAI-1 in the peripheral blood in 57 MDD patients pre- and post-treatment and in 57 healthy controls. We verified that BDNF and tPA levels were significantly decreased, whereas proBDNF and PAI-1 levels elevated obviously in MDD group pre-treatment. And after 4 weeks SSRIs treatment, the BDNF and tPA levels increased while the proBDNF and PAI-1 levels reduced. The MDD pre-treatment group had the lowest ratio of BDNF to proBDNF compared to MDD post-treatment group and control group. Though the ratio of tPA/PAI-1 in MDD pre-treatment had not reached the significance, it was still the lowest one among the three groups. The combination of tPA + PAI + BDNF showed the best diagnostic value for MDD. In summary, our data suggested that the interaction between tPA and PAI-1 implicated to the MDD and the antidepressant treatment which might through regulating the BDNF/proBDNF ratio. The combination of tPA, PAI-1 and BDNF might offer a helpful way for MDD diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: There is a significant lack of therapeutic options for mild cognitive impairment (MCI), which is rapidly becoming a global epidemic due to aging. Transcranial photobiomodulation (t-PBM) involves delivering near-infrared light (NIR) to the scalp, targeting cortical areas of the brain. NIR t-PBM has recently emerged as a potential therapy for various neurodegenerative conditions, including memory issues., Aims: This study aimed to evaluate cognition scores (primary outcome), depression, anxiety, resilience scores, neuroplasticity, and neurodegeneration biomarkers (secondary outcomes) in individuals with MCI undergoing t-PBM therapy or receiving a placebo., Materials and Methods: A total of 93 older adult individuals with MCI were randomly assigned to either a t-PBM (n = 47) or Placebo (n = 46) group. Clinical assessments were conducted at baseline, 60 days post-treatment, and a 150-day follow-up. We also measured serum levels of brain-derived neurotrophic factor (BDNF), a neuroplasticity biomarker, as well as neuron-specific enolase (NSE) and calcium-binding protein B (S100B), which are neurodegeneration biomarkers. Intervention effects were analyzed using repeated measures (RM) two-way ANOVA followed by Tukey post hoc test. Fischer's exact test and Generalized Estimating Equations (GEE) were also applied., Results: Of the 93 older adults individuals invited to participate, 76 (t-PBM: 40, placebo: 36) completed the study. The t-PBM significantly improved cognition as measured by the Montreal Cognitive Assessment (MoCA) compared to placebo (p = 0.0301). The delta values for MoCA scores were 3.20 in the t-PBM group and 1.97 in the placebo group. This effect persisted until the three-month follow-up, accompanied by increased BDNF levels in the t-PBM group but not in the placebo group (p = 0.0046). The delta values for BDNF were 821.94 in the t-PBM group and 359.41 in the placebo group. t-PBM did not alter depression, anxiety, resilience scores, nor the levels of NSE and S100B in individuals with MCI., Conclusion: The t-PBM increases cognitive function and BDNF levels in adults with MCI. Its application as an adjunctive treatment may play a crucial role in preventing neurodegenerative diseases., Competing Interests: Declaration of competing interest Dr. Cassano consulted for Janssen Research and Development and for Niraxx Inc.; he was funded by PhotoThera Inc., LiteCure LLC. and Cerebral Sciences Inc. to conduct studies on transcranial photobiomodulation; is a shareholder of Niraxx Inc.; and has filed several patents related to the use of near infrared light in psychiatry. All other authors declare that they do not have any known competing financial interests or personal relationships that could influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study assessed whether polyphenolic rich supplement containing Bacopa monnieri (BM: 300 mg), Panax quinquefolius ginseng (PQ: 100 mg) and whole coffee fruit extract (WCFE: 100 mg) could enhance cognitive performance, affect and cerebral-cortical activation over 28-days of intervention. Method: A randomised, double-blind, placebo-controlled, between-group study of 52 healthy adults between 35 and 65 years (M = 50.20, SD = 9.37) was conducted. Measures of cognition, affect and brain activity were measured at three time points: baseline, 28 days post intervention and 14 days post washout. At each time point, haemodynamic response in the prefrontal cortex (PFC) was measured using functional near-infrared spectroscopy (fNIRS), and serum brain-derived neurotrophic factor (BDNF). Results: The polyphenolic-rich supplement reliably improved positive affect and delayed recall compared to placebo following 28 days of supplementation. For the brain, those in the active condition showed greater PFC activation on performance of the 2-back tasks post supplementation compared to placebo ( p  < .05, d = 0.6). Discussion: This is the first report of a 28-day supplement intervention and 2-week follow-up study to assess changes in affect, cognition, cerebral haemodynamic response and BDNF in healthy middle-aged adults. The potential synergistic effects of polyphenolic compounds on neurocognitive function in middle-aged adults through emotional-cognitive processing and cognitive reserve are important for promoting brain and cognitive health.

This study compared the effects of linear (LP) and nonlinear (NLP) training periodization on cognitive functions, neurotrophic biomarkers [plasma brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)], and cathepsin-B in patients with coronary artery disease (CAD). Forty-four patients with CAD reported to our laboratory on two occasions to undergo testing procedures before and after training sessions, and were then blindly randomized to NLP or LP for 36 training sessions. Visit 1 included blood samples and a maximal cardiopulmonary exercise testing to get maximal oxygen uptake (V̇o 2peak ). Visit 2 included cognitive functions assessment. Thirty-nine patients completed the study (LP: n = 20, NLP: n = 19), with no observed changes in cognitive performances after the training intervention in either group. IGF-1 concentration decreased in both groups (time-effect: P < 0.001), whereas BDNF concentration increased (time-effect: P < 0.05) without group interaction, and cathepsin-B did not change after the intervention. Associations were found between ΔV̇o 2peak and ΔBDNF ( R 2 = 0.18, P = 0.04), and ΔIGF-1 and Δshort-term/working memory ( R 2 = 0.17, P = 0.01) in the pooled sample, with ΔIGF-1 and ΔBDNF accounting for 10% of the variance in Δshort-term/working memory. In the LP group, associations were found between ΔV̇o 2peak and ΔBDNF ( R 2 = 0.45, P = 0.02), ΔBDNF and Δshort-term/working memory ( R 2 = 0.62, P = 0.004), ΔIGF-1 and Δshort-term/working memory ( R 2 = 0.31, P = 0.01), and ΔIGF-1 and Δexecutive function ( R 2 = 0.22, P = 0.04). This study indicates that linear and nonlinear training periodization led to an increase in BDNF, and a decrease in IGF-1, without change in cognitive function in individuals with stable CAD. NEW & NOTEWORTHY We used a novel and supervised iso-energetic training, integrating both moderate- and high-intensity aerobic exercises. Our findings indicate that greater variation in training load did not yield cognitive enhancements, although both protocols exhibited positive effects on brain-derived neurotrophic factor (BDNF) levels. Moreover, this study establishes a clear positive association between short-term and working memory and neurotrophic biomarkers. In addition, the independent predictive value of change in insulin-like growth factor-1 (IGF-1) on improvement in short-term and working memory highlight the close relationship between neurotrophic markers and cognition. Consequently, our results advocate for exercise training interventions targeting neurotrophic biomarkers to enhance cognitive function among individuals with coronary artery disease.

Abstract: Baumgartner, NW, Belbis, MD, Kargl, C, Holmes, MJ, Gavin, TP, Hirai, DM, and Kao, S-C. Acute effects of high-intensity resistance exercise on recognition of relational memory, lactate, and serum and plasma brain-derived neurotrophic factor. J Strength Cond Res 38(11): 1867-1878, 2024-Acute aerobic exercise improves memory, but this phenomenon is understudied in response to resistance exercise (RE) despite evidence that RE-induced increases in lactate and brain-derived neurotrophic factor (BDNF) play mechanistic roles in memory performance. To determine the acute effect of RE on lactate, BDNF, and their associations with object and relational memory, blood lactate, and serum and plasma BDNF were taken from 36 adults (average age 23.64 ± 3.89 years; 18 woman) before and immediately after 42 minutes of high-intensity RE and a rest condition on counterbalanced days. Subjects then immediately studied a series of paired objects and completed object and relational recognition tasks. Results revealed a condition by trial interaction, previously studied objects were remembered less accurately following RE ( d = 0.66) but recognition occurred faster ( d = 0.28), indicating a speed-accuracy tradeoff following RE. There was no effect of either intervention on relational recognition performance. Lactate ( d = 3.68) and serum BDNF ( d = 0.74) increased following RE, whereas there was no time-related change in lactate and serum BDNF following rest. However, changes in lactate and BDNF did not predict any measures of object ( rs < 0.25, p s > 0.16) or relation recognition ( rs < 0.28, p s > 0.13). Collectively, these findings suggest that acute high-intensity RE selectively improves the processing speed of recognizing objects at the cost of less accurate recognition of previously studied objects. Furthermore, changes in object and relational memory performance are unlikely driven by acute increases in lactate or BDNF following high-intensity RE., (Copyright © 2024 National Strength and Conditioning Association.)