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Sleep's crucial role in memory consolidation is well-established, with neuroimaging and sleep stage analysis revealing the intricate processes involved. Sleep deprivation significantly impairs memory performance and the ability to form new memories, highlighting the need for effective countermeasures. This article concludes that while sleep deprivation significantly impairs memory, the emerging insights into the gut-brain axis offer a promising frontier for developing novel interventions that can mitigate these effects. The review discusses various interventions, ranging from pharmaceutical compounds like donepezil, memantine, and tolcapone, to innovative physical therapy techniques such as transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and transcranial direct current stimulation (tDCS). Additionally, the emerging role of the gut-brain axis in sleep deprivation-induced memory impairment is examined, shedding light on the complex interplay between gut microbiota and cognitive functions. This comprehensive review explores the multifaceted relationship between sleep deprivation and memory impairment, delving into the neurobiological mechanisms underlying these processes and examining potential interventions. [ABSTRACT FROM AUTHOR]

Global cerebral ischemia is one of the major causes of memory and cognitive impairment. Hyperactivation of acetylcholine esterase (AChE), oxidative stress, and inflammation are reported to cause memory and cognitive impairment in global cerebral ischemia. Morin, a flavonoid, is reported to have neuroprotective properties through its antioxidant and anti-inflammatory in multiple neurological diseases. However, its neuroprotective effects and memory and cognition enhancement have not yet been investigated. In the present study, we have determined the memory and cognition, and neuroprotective activity of Morin in bilateral common carotid artery occlusion and reperfusion (BCCAO/R) in Wistar rats. We found that Morin treatment significantly improved motor performance like grip strength and rotarod. Further, Morin improved memory and cognition in BCCAO rats by decreasing the AchE enzyme activity and enhancing the acetylcholine (Ach) levels. Additionally, Morin exhibited neuroprotection by ameliorating oxidative stress, neuroinflammation, and apoptosis in BCCAO rats. These findings confirm that Morin could enhance memory and cognition by ameliorating AchE activity, oxidative stress, neuroinflammation, and apoptosis in global cerebral ischemia. Therefore, Morin could be a promising neuroprotective and memory enhancer against global cerebral ischemic injury. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by impaired insulin/insulin-like growth factor-1 signaling in the hippocampus. Zeaxanthin and lutein, known for their antioxidant and anti-inflammatory properties, have been reported to protect against brain damage and cognitive decline. However, their mechanisms related to insulin signaling in AD remain unclear. This study investigated the efficacy and mechanisms of zeaxanthin, lutein, and resveratrol in modulating an AD-like pathology in an amyloid-β rat model. Rats were administered hippocampal infusions of 3.6 nmol/day amyloid-β (Aβ)(25-35) for 14 days to induce AD-like memory deficits (AD-CON). Normal control rats received Aβ(35-25) (Normal-CON). All rats had a high-fat diet. Daily, AD rats consumed 200 mg/kg body weight of zeaxanthin (AD-ZXT), lutein (AD-LTN), and resveratrol (AD-RVT; positive-control) or resistant dextrin as a placebo (AD-CON) for eight weeks. The AD-CON rats exhibited a higher Aβ deposition, attenuated hippocampal insulin signaling (reduced phosphorylation of protein kinase B [pAkt] and glycogen synthase kinase-3β [pGSK-3β]), increased neuroinflammation, elevated acetylcholinesterase activity, and memory deficits compared to the Normal-CON group. They also showed systemic insulin resistance and high hepatic glucose output. Zeaxanthin and lutein prevented memory impairment more effectively than the positive-control resveratrol by suppressing acetylcholinesterase activity, lipid peroxidation, and pro-inflammatory cytokines (TNF-α, IL-1β). They also potentiated hippocampal insulin signaling and increased brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CTNF) mRNA expression to levels comparable to the Normal-CON rats. Additionally, zeaxanthin and lutein improved glucose disposal, reduced hepatic glucose output, and normalized insulin secretion patterns. In conclusion, zeaxanthin and lutein supplementation at doses equivalent to 1.5–2.0 g daily in humans may have practical implications for preventing or slowing human AD progression by reducing neuroinflammation and maintaining systemic and central glucose homeostasis, showing promise even when compared to the established neuroprotective compound resveratrol. However, further clinical trials are needed to evaluate their efficacy and safety in human populations. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the benefit of verapamil on stress-induced memory impairment in mice. Methods: Forty-eight (48) mice were used in this study. They were divided into two equal groups based on the two models of stress used in this study (sleep deprivation and hypoxia). Each model was further divided into 4 groups of six animals each. The mice in the sleep deprivation model were suspended on a platform above water while in the hypoxic model, mice were locked in an airless container for 20 min daily throughout the experiment. As for the intervention, 25 and 50 mg/kg verapamil were preadministered via the oral route to study groups, except the normal control group and negative control group in both models. After seven-day stress and intervention, the mice were subjected to behavioural tests (Y-maze and object recognition tests), biochemical assays (for acetylcholinesterase activity) and histochemical analysis. Results: Stress caused a significant (p < 0.05) impairment in the consolidation and retrieval of working and recognition memories. Also, acetylcholinesterase activity was significantly (p < 0.05) enhanced in the stressed groups when compared to control groups. Similarly, the histological analysis revealed a significant decline in population (p < 0.05), distribution and density of viable neurons in specific areas of the hippocampus and prefrontal cortex. These alterations were significantly (p < 0.05) attenuated in verapamil-treated groups almost in a dose-dependent pattern. Conclusion: Verapamil displays significant memory-enhancing effects in two (2) murine models of stress. Antihypertensives should therefore be considered a viable prospect in the management of stress-related memory disorders after additional studies have been done to establish the mechanisms of action. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to evaluate the association between memory impairment and its risk and protective factors, focusing on demographic and health-related variables among older adults in Indonesia. Method: The data analyzed were the Indonesian Family Life Survey-5 (IFLS-5) using cross-sectional variables of 4236 older adults aged 60 years and over included in the 2015 round. Memory impairment was assessed by immediate word list recall from the Telephone Interview for Cognitive Status (TICS). Sociodemographic factors and multiple health variables were included as predictors. Data were analyzed using frequency analyses bivariate and stepwise logistic regression tests. Result: Among 4236 older adults, 49.7% were male and 50.3% were female. Stepwise backward analyses showed that memory impairment was independently associated with older age, being female, or not in a union (unmarried, separated, divorced, or widowed), having obtained low levels of education, living in a rural area, reporting low life satisfaction, low social capital, higher dependency, and having clinical depression. Only moderate (but not high or low) physical activity levels were associated with a lower risk. Being underweight increased the risk, but being overweight/obese (as assessed by BMI) protective factors for a lower immediate recall score. Conclusion: Increasing education and continued engagement of older adults in psychosocial activities, including moderate physical activity, improving mental health, preventing weight loss, and maintaining functional ability to decrease dependency, are associated with increased episodic memory, especially in non-married and older women in rural areas of Indonesia. [ABSTRACT FROM AUTHOR]

Background: Childhood exercise enhances brain structure, while diabetes detrimentally affects it. This study examines early-life exercise's influence on adult diabetic rats' memory and neuroplasticity. Methods: Male Wistar pups were divided into Control, Diabetes, Exercise Training, and Diabetes exercise groups. Diabetes was induced on day 23 with Alloxan (200 mg/kg). A 3-week regimen included aerobic and resistance training thrice weekly. The aerobic intensity was 70%, and resistance varied from 50% to 100% of the maximal carrying capacity (MCC). Following the last training sessions, spatial memory and retrieval tests were performed in infancy, childhood, and emerging adulthood using the Morris Water Maze test (MWM). The hippocampus was excised to measure protein and gene expression of brain-derived neurotrophic factor (BDNF), calmodulin-dependent protein kinase (CAMKII), N-methyl-D-aspartate receptors (NMDAR), and cAMP-response element-binding protein (CREB) by western blotting and reverse transcription–polymerase-chain reaction (RT-PCR) methods. Blood samples were collected during each developmental stage to measure glucose levels, at the study's conclusion, to assess Interleukin-1β levels using the ELISA method. The Nissel staining assessed dead hippocampal cells in CA1. Results: Post-natal exercise improved spatial memory (p < 0.05) and glucose levels (p < 0.05) in diabetic rats during adolescence and emerging adulthood. Despite reduced mRNA expression (NMDAR 40%, BDNF 62%, CREB 43%, CAMKII 66%), diabetic rats, by study end, showed increased BDNF, NMDARR, CAMKII, CREB protein/gene expression (p < 0.05) in emerging adulthood for both training groups. Conclusion: Early-life exercise influenced hippocampal BDNF/NMDAR-CAMKII/CREB pathways in a diabetic rat model, highlighting post-natal exercise's role in neuroplasticity memory enhancement and improved glucose level. [ABSTRACT FROM AUTHOR]

MDD often brings about numerous health challenges and disruptions, with memory loss emerging as a prominent concern. Many studies have tried to find the relationship between MDD and the patients' memory functions. Research has shown that depression affects memory encoding in a variety of significant ways. This paper analyzes research articles and relevant literature from 2000 to 2023 to connect the effects of depression to symptoms of memory loss. The included studies cover the effects on various types of memory encoding for patients either under depression or in remitted depression throughout differing age cohorts. Research methods include testing on source memory, RCFT (Rey-Osterrieth-Complex-Figure-Test), and learning and recall. Overall, depression leads to many negative effects on retention even when a patient is in remission including deficits in contextual cognitive memory, both verbal and non-verbal memory, and working memory. Depression patients have difficulties during the encoding process, which causes impairments of these memories. Giving patients extra cognitive support can help lessen the deficits. However, the problem alters with aging, memory kinds, the number of past depressive episodes, and other control factors. [ABSTRACT FROM AUTHOR]

The increasing prevalence of age-related neurodegenerative disorders owing to the aging population worldwide poses substantial challenges. This study investigated the neuroprotective effects of protocatechuic acid (PCA), a compound found in various fruits, vegetables, and grains, using a scopolamine-induced hypomnesia mouse model. Six-week-old male C57BL/6J mice were orally administered PCA at doses of 10 and 100 mg/kg body weight per day for two weeks, along with intraperitoneal injections of scopolamine. Learning and memory abilities were assessed using the passive avoidance, Morris water maze, and Y-maze behavioral assays. Biochemical analyses evaluated the levels of oxidative stress markers, including 8-hydroxydeoxyguanosine (8-OHdG) in the blood and malondialdehyde (MDA) in the brain, as well as phase II antioxidant proteins in the hippocampus. Histological examination was conducted to determine hippocampal integrity. Our results demonstrated that PCA administration at 10 mg/kg body weight per day or higher for two weeks (i) significantly ameliorated scopolamine-induced learning and memory impairments, as evidenced by improved performance in behavioral tasks, (ii) reduced plasma 8-OHdG levels and cerebral MDA levels in a dose-dependent manner, (iii) increased antioxidant protein expressions in the hippocampal tissue, and (iv) mitigated histological damage in the hippocampal region of the brain. These findings suggest that oral administration of PCA provides neuroprotective effects against oxidative stress-induced learning and memory impairments, possibly through upregulating antioxidant machinery. Therefore, PCA may serve as a promising dietary supplement for mitigating cognitive deficits associated with neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are characterized by progressive memory impairment and cognitive decline. This review aims to unravel the molecular mechanisms involved in the enhancement of memory function and mitigation of memory impairment through the activation of PPARγ agonists in neurodegenerative diseases. The findings suggest that PPARγ agonists modulate various molecular pathways involved in memory formation and maintenance. Activation of PPARγ enhances synaptic plasticity, promotes neuroprotection, suppresses neuroinflammation, attenuates oxidative stress, and regulates amyloid-beta metabolism. The comprehensive understanding of these molecular mechanisms would facilitate the development of novel therapeutic approaches targeting PPARγ to improve memory function and ultimately to alleviate the burden of neurodegenerative diseases. Further research, including clinical trials, is warranted to explore the efficacy, safety, and optimal use of specific PPARγ agonists as potential therapeutic agents in the treatment of memory impairments associated with neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Mice transgenic for human P301S tau protein exhibit many characteristics of the human tauopathies, including the formation of abundant hyperphoshorylated tau filaments, the associated neuroinflammation and disease phenotype. However, the exact underpinning mechanisms are still not fully addressed that hinder our understanding of the tauopathy diseases and the development of possible therapeutic targets.Methods: In the current study, hippocampus from three disease time points (2, 4 and 6 months) of P301S mice were further characterized in comparison to the age and sex matched control wild type mice (WT) that do not express the transgene. Different spectrum of hippocampal dependent cognitive tests, biochemical and pathological analysis were conducted to understand the disease progression and the associated changes in each stage. Results: Cognitive impairment was manifested as early as 2 months age, prior to the identification of tau aggregation and phosphorylation by immunostaining. P301S mice manifested an increased pro-inflammatory related changes at mRNA transcription level (IL-1b and IL17A) with the progression of the disease and when compared to the WT mice of the same age. Among the identified genes in the current study, the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) genes expression that is considered as the master regulator of an endogenous inducible defense system was significantly impaired in P301S mice by 4 and 6 months when compared to healthy WT controls. A data that was also supported by the immunostaining of the serial brain sections including the both brain stem and hippocampus. The current result is suggesting that the downregulation of Nrf2 gene and the impaired Nrf2 dependent anti-inflammatory mechanisms in P301S mice brain is possibly contributing -among other factors- in the neuroinflammation and tauopathy, and that modulation of Nrf2 signaling impairments can be further investigated as a promising potential therapeutic target for tauopathy. [ABSTRACT FROM AUTHOR]

Obesity is a chronic disease caused by excessive fat accumulation that impacts the body and brain health. Insufficient leptin or leptin receptor (LepR) is involved in the disease pathogenesis. Leptin is involved with several neurological processes, and it has crucial developmental roles. We have previously demonstrated that leptin deficiency in early life leads to permanent developmental problems in young adult mice, including an imbalance in energy homeostasis, alterations in melanocortin and the reproductive system and a reduction in brain mass. Given that in humans, obesity has been associated with brain atrophy and cognitive impairment, it is important to determine the long-term consequences of early-life leptin deficiency on brain structure and memory function. Here, we demonstrate that leptin-deficient (Lep Ob) mice exhibit altered brain volume, decreased neurogenesis and memory impairment. Similar effects were observed in animals that do not express the LepR (LepRNull). Interestingly, restoring the expression of LepR in 10-week-old mice reverses brain atrophy, in addition to neurogenesis and memory impairments in older animals. Our findings indicate that leptin deficiency impairs brain development and memory, which are reversible by restoring leptin signalling in adulthood. [ABSTRACT FROM AUTHOR]

Background: Research work has shown that hippocampal subfields are atrophic to varying extents in multiple sclerosis (MS) patients. However, studies examining the functional implications of subfield-specific hippocampal damage in early MS are limited. We aim to gain insights into the relationship between hippocampal atrophy and memory function by investigating the correlation between global and regional hippocampal atrophy and memory performance in early MS patients. Methods: From the Italian Neuroimaging Network Initiative (INNI) dataset, we selected 3D-T1-weighted brain MRIs of 219 early relapsing remitting (RR)MS and 246 healthy controls (HC) to identify hippocampal atrophic areas. At the time of MRI, patients underwent Selective-Reminding-Test (SRT) and Spatial-Recall-Test (SPART) and were classified as mildly (MMI-MS: n.110) or severely (SMI-MS: n:109) memory impaired, according to recently proposed cognitive phenotypes. Results: Early RRMS showed lower hippocampal volumes compared to HC (p < 0.001), while these did not differ between MMI-MS and SMI-MS. In MMI-MS, lower hippocampal volumes correlated with worse memory tests (r = 0.23–0.37, p ≤ 0.01). Atrophic voxels were diffuse in the hippocampus but more prevalent in cornu ammonis (CA, 79%) than in tail (21%). In MMI-MS, decreased subfield volumes correlated with decreases in memory, particularly in the right CA1 (SRT-recall: r = 0.38; SPART: r = 0.34, p < 0.01). No correlations were found in the SMI-MS group. Conclusion: Hippocampal atrophy spreads from CA to tail from early disease stages. Subfield hippocampal atrophy is associated with memory impairment in MMI-MS, while this correlation is lost in SMI-MS. This plays in favor of a limited capacity for an adaptive functional reorganization of the hippocampi in MS patients. [ABSTRACT FROM AUTHOR]

Summary: Sleep disturbances are prevalent in Alzheimer's disease (AD), affecting individuals during its early stages. We investigated associations between subjective sleep measures and cerebrospinal fluid (CSF) biomarkers of AD in adults with mild cognitive symptoms from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study, considering the influence of memory performance. A total of 442 participants aged >50 years with a Clinical Dementia Rating (CDR) score of 0.5 completed the Pittsburgh Sleep Quality Index questionnaire and underwent neuropsychological assessment, magnetic resonance imaging acquisition, and CSF sampling. We analysed the relationship of sleep quality with CSF AD biomarkers and cognitive performance in separated multivariate linear regression models, adjusting for covariates. Poorer cross‐sectional sleep quality was associated with lower CSF levels of phosphorylated tau and total tau alongside better immediate and delayed memory performance. After adjustment for delayed memory scores, associations between CSF biomarkers and sleep quality became non‐significant, and further analysis revealed that memory performance mediated this relationship. In post hoc analyses, poorer subjective sleep quality was associated with lesser hippocampal atrophy, with memory performance also mediating this association. In conclusion, worse subjective sleep quality is associated with less altered AD biomarkers in adults with mild cognitive symptoms (CDR score 0.5). These results could be explained by a systematic recall bias affecting subjective sleep assessment in individuals with incipient memory impairment. Caution should therefore be exercised when interpreting subjective sleep quality measures in memory‐impaired populations, emphasising the importance of complementing subjective measures with objective assessments. [ABSTRACT FROM AUTHOR]

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Background: Chemobrain is widespread in breast cancer patients receiving chemotherapy. However, the exact mechanism, especially the associated signalling pathway, is not currently clear. This study was to evaluate the behavioural changes in breast cancer mice after chemotherapy and to further explore the role of Wnt3a/glycogen synthase kinase (GSK3β)/β-catenin signalling in chemobrain. Methods: MMTV-PyMT(+) breast cancer mice were injected intraperitoneally with doxorubicin (4 mg/kg) once a week for three weeks to establish a chemobrain model. The Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess the learning and memory ability. Electron microscopy was used to observe the structural changes in the hippocampal CA1 region. The brain tissue of breast cancer mice after chemotherapy was taken out for mRNA-seq detection. Then, the expression levels and phosphorylation of key proteins in the Wnt3a/GSK3 β/β-catenin signalling pathway were evaluated through Western blotting (WB) and immunofluorescence. Results: Doxorubicin-induced spatial and short-term memory impairment was observed in breast cancer mice, and obvious neuronal damage could be seen in the hippocampal CA1 region. Immunofluorescence staining for GSK3β was increased. Wnt signalling pathway is highly enriched from mRNA-seq analysis, with GSK3β genes at important nodes. The relative protein levels of p-PI3K, p-AKT, p-GSK3 β, Wnt3a and TCF-1 were decreased significantly, while the p-β-catenin level was increased. After injection of the GSK3β inhibitor sb216763 (1 ng/0.5 µl/side), hippocampal neuronal injury was alleviated to some extent, and the changes in the expression of proteins upstream and downstream of this signalling pathway were reversed. Conclusion: Wnt3a/GSK3 β/β-catenin signalling is likely involved in doxorubicin-induced memory impairment. This result provides basic evidence for the further study of chemobrain in breast cancer. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cardiac surgery is associated with various durations of cerebral autoregulation (CA) impairment and can significantly impact cognitive function. Cognitive functions such as memory, psychomotor speed, and attention are significantly impacted after cardiac surgery, necessitating prioritization of these areas in cognitive function tests. There is a lack of research connecting cerebral autoregulation impairment to specific cognitive function domains after cardiac surgery. This study aimed to determine if impaired cerebral autoregulation is associated with postoperative memory impairment and to test the hypothesis that the duration of this impairment affects the development of postoperative memory issues. Materials and Methods: A prospective study was conducted in 2021–2023. After approval of the Ethics Committee and with patient's written consent, 83 adult patients undergoing elective on-pump coronary artery bypass graft (CABG) surgery were enrolled. All patients were assessed for cognitive function 1 day before surgery using the Mini-Mental state examination (MMSE-2) test as a screening tool and the Hopkins Verbal Learning Test-Revised (HVLT-R) to assess memory specifically. To diagnose possible memory impairment (IM), all patients underwent a repeat assessment of cognitive function on the 7th–10th postoperative day. Cerebral autoregulation monitoring using transcranial Doppler was performed. Cerebral autoregulation status index (Mx) was recorded using Intensive Care Brain Monitoring System software, 9.1.5.23 (Cambridge, UK). Results: According to our research, the incidence of postoperative memory impairment is 30.1%. Temporary cerebral autoregulation impairment occurs in all patients undergoing elective in-pump CABG surgery. The duration of the single longest CA impairment event in seconds (LCAI) and the LCAI dose were higher in patients with postoperative memory impairment, p = 0.006 and p < 0.007, respectively. Conclusions: Cerebral autoregulation impairment is important in developing memory loss after cardiac surgery. The duration and dose of the LCAI event are predictive of postoperative memory impairment. [ABSTRACT FROM AUTHOR]

Lead (Pb) is a common environmental neurotoxicant that results in abnormal neurobehavior and impaired memory. Avicularin (AVL), the main dietary flavonoid found in several plants and fruits, exhibits neuroprotective and hepatoprotective properties. In the present study, the effects of AVL on Pb-induced neurotoxicity were evaluated using ICR mice to investigate the molecular mechanisms behind its protective effects. Our study has demonstrated that AVL treatment significantly ameliorated memory impairment induced by lead (Pb). Furthermore, AVL mitigated Pb-triggered neuroinflammation, ferroptosis, and oxidative stress. The inhibition of Pb-induced oxidative stress in the brain by AVL was evidenced by the reduction in malondialdehyde (MDA) levels and the enhancement of glutathione (GSH) and glutathione peroxidase (GPx) activities. Additionally, in the context of lead-induced neurotoxicity, AVL mitigated ferroptosis by increasing the expression of GPX4 and reducing ferrous iron levels (Fe2+). AVL increased the activities of glycogenolysis rate-limiting enzymes HK, PK, and PYG. Additionally, AVL downregulated TNF-α and IL-1β expression while concurrently enhancing the activations of AMPK, Nrf2, HO-1, NQO1, PSD-95, SNAP-25, CaMKII, and CREB in the brains of mice. The findings from this study suggest that AVL mitigates the memory impairment induced by Pb, which is associated with the AMPK/Nrf2 pathway and ferroptosis. [ABSTRACT FROM AUTHOR]

Abstract Mice transgenic for human P301S tau protein exhibit many characteristics of the human tauopathies, including the formation of abundant hyperphoshorylated tau filaments, the associated neuroinflammation and disease phenotype. However, the exact underpinning mechanisms are still not fully addressed that hinder our understanding of the tauopathy diseases and the development of possible therapeutic targets.Methods: In the current study, hippocampus from three disease time points (2, 4 and 6 months) of P301S mice were further characterized in comparison to the age and sex matched control wild type mice (WT) that do not express the transgene. Different spectrum of hippocampal dependent cognitive tests, biochemical and pathological analysis were conducted to understand the disease progression and the associated changes in each stage. Results: Cognitive impairment was manifested as early as 2 months age, prior to the identification of tau aggregation and phosphorylation by immunostaining. P301S mice manifested an increased pro-inflammatory related changes at mRNA transcription level (IL-1b and IL17A) with the progression of the disease and when compared to the WT mice of the same age. Among the identified genes in the current study, the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) genes expression that is considered as the master regulator of an endogenous inducible defense system was significantly impaired in P301S mice by 4 and 6 months when compared to healthy WT controls. A data that was also supported by the immunostaining of the serial brain sections including the both brain stem and hippocampus. The current result is suggesting that the downregulation of Nrf2 gene and the impaired Nrf2 dependent anti-inflammatory mechanisms in P301S mice brain is possibly contributing -among other factors- in the neuroinflammation and tauopathy, and that modulation of Nrf2 signaling impairments can be further investigated as a promising potential therapeutic target for tauopathy.

Abstract Computational intelligence techniques have emerged as a promising approach for diagnosing various medical conditions, including memory impairment. Increased abuse of psychoactive drugs poses a global public health burden, as repeated exposure to these substances can cause neurodegeneration, premature aging, and negatively affect memory impairment. Many studies in the literature relied on statistical studies, but they remained inaccurate. Some studies relied on physical data because the time factor was not considered, until Artificial Intelligence (AI) techniques came along that proved their worth in this diagnosis. The variable deep neural network method was used to adapt to the intermediate results and re-process the intermediate in case the result is undesirable. Computational intelligence was used in this study to classify a brain image from MRI or CT scans and to show the effectiveness of the dose ratio on health with treatment time, and to diagnose memory impairment in users of psychoactive substances. Understanding the neurotoxic profiles of psychoactive substances and the underlying pathways is hypothesized to be of great importance in improving the risk assessment and treatment of substance use disorders. The results proved the worth of the proposed method in terms of the accuracy of recognition rate as well as the possibility of diagnosis. It can be concluded that the diagnostic efficiency is increased by increasing the number of hidden layers in the neural network and controlling the weights and variables that control the deep learning algorithm. Thus, we conclude that good classification in this field may save human life or early detection of memory impairment.

Objective: To explore the intrinsic mechanism of enriched environment- induced improvement of memory in rats with chronic cerebral ischemia. Method: Forty-eight healthy male SD rats were randomly divided into chronic cerebral ischemia+standard environment group (CCH+SE), chronic cerebral ischemia+rich environment group (CCH+EE), and Sham surgery+ standard environment group (Sham+SE) with 16 rats in each group. The CCH+SE group and CCH+EE group were given bilateral common carotid artery ligation surgery and a rat model of chronic cerebral ischemia was constructed. The Sham+SE group performed the same procedures as the model group without ligating bilateral common carotid arteries. Three groups of rats were raised in corresponding environments for 21 days, and their spatial learning and memory functions were tested using a water maze test. Protein immunoblotting and immunofluorescence techniques were used to detect changes of BDNF, GAP-43, and SYN proteins expressions in the CA3 region of the rat hippocampus. Result: Compared with the standard environment group, the learning and memory functions of the enriched environment group were significantly improved, with a statistically significant difference (P<0.05). The expression levels of BDNF, GAP-43, and SYN proteins in the CA3 region of the hippocampus were significantly increased, with a statistically significant difference (P<0.05). Conclusion: Enriched environment intervention can improve learning and memory ability in rats with chronic cerebral ischemia, and its underlying mechanism may be promoting synaptic remodeling in the hippocampal CA3 region. [ABSTRACT FROM AUTHOR]

Neuroinflammation may play an important role in the development of Alzheimer's disease (AD). Previous studies have reported that lipopolysaccharide (LPS)‐induced neuroinflammation causes memory impairments and behavioral disorders. We investigated the potential preventive effects of punicalin (PUN), a polyphenolic component of pomegranate, on LPS‐induced memory deficiency and anxiety‐ and depression‐like behaviors, along with the underlying mechanisms. LPS‐treated cultured microglial BV2 cells and BV2 cell/Neuro‐2a (N2a) cell coculture system were investigated for anti‐neuroinflammatory effects of PUN in vitro. The in vivo experiments involved mice administered a 4‐week course of oral gavage with 1500 mg/kg/d PUN before intraperitoneal LPS (250 mg/kg daily 7 times) injections. The in vitro results demonstrated that PUN inhibited the LPS‐induced inflammatory cytokine (IL‐18, IL‐1β, TNF‐ɑ, and IL‐6) production in BV2 cells and protected N2a cells from synaptic damage mediated by BV2 microglia‐induced neuroinflammation. In in vivo studies, it was observed that PUN improved memory impairment and anxiety‐ and depression‐like behaviors caused by LPS and reduced the expression of inflammatory proteins such as iNOS, COX‐2, IL‐1β, IL‐2, IL‐6, and TNF‐α. Furthermore, PUN inhibited the LPS‐induced production of MDA; increased the activities of CAT, SOD, and GSH‐Px, and inhibited LPS‐induced Aβ1−42 generation through down‐regulation of APP and BACE1 expression. Moreover, PUN also suppressed the expression of TLR4, IRAK4, TRAF6, IKK‐β, NF‐κB, p65, and HMGB1 in LPS‐treated mouse brain and cultured microglial BV‐2 cells. These results suggest that PUN inhibits LPS‐induced memory impairment via anti‐inflammatory and anti‐amylogenic mechanisms through inhibition of TLR4‐NF‐kB activation. [ABSTRACT FROM AUTHOR]

Computational intelligence techniques have emerged as a promising approach for diagnosing various medical conditions, including memory impairment. Increased abuse of psychoactive drugs poses a global public health burden, as repeated exposure to these substances can cause neurodegeneration, premature aging, and negatively affect memory impairment. Many studies in the literature relied on statistical studies, but they remained inaccurate. Some studies relied on physical data because the time factor was not considered, until Artificial Intelligence (AI) techniques came along that proved their worth in this diagnosis. The variable deep neural network method was used to adapt to the intermediate results and re-process the intermediate in case the result is undesirable. Computational intelligence was used in this study to classify a brain image from MRI or CT scans and to show the effectiveness of the dose ratio on health with treatment time, and to diagnose memory impairment in users of psychoactive substances. Understanding the neurotoxic profiles of psychoactive substances and the underlying pathways is hypothesized to be of great importance in improving the risk assessment and treatment of substance use disorders. The results proved the worth of the proposed method in terms of the accuracy of recognition rate as well as the possibility of diagnosis. It can be concluded that the diagnostic efficiency is increased by increasing the number of hidden layers in the neural network and controlling the weights and variables that control the deep learning algorithm. Thus, we conclude that good classification in this field may save human life or early detection of memory impairment. [ABSTRACT FROM AUTHOR]

Alcohol consumption is known to have detrimental effects on memory function, with various studies implicating ethanol in the impairment of cognitive processes related to memory retention and retrieval. This review aims to elucidate the complex neurobiological mechanisms underlying ethanol-induced memory impairment. Through a thorough search of existing literature using electronic databases, relevant articles focusing on the neurobiological mechanisms of ethanol on memory were identified and critically evaluated. This review focuses on the molecular and neural pathways through which ethanol exerts its effects on memory formation, consolidation, and recall processes. Key findings from the included studies shed light on the impact of ethanol on neurotransmitter systems, synaptic plasticity, and neuroinflammation in relation to memory impairment. This review contributes to a better understanding of the intricate mechanisms by which alcohol impairs memory function, offering insights for future research directions and the development of targeted interventions to alleviate these cognitive impairments. [ABSTRACT FROM AUTHOR]

[Display omitted] • Chronic Unpredictable mild stress (CUMS) increased serum Corticosterone level. • UCMS increased oxidative stress status and neuro-inflammation and decreasing BDNF and Ki67 in the brain. • Oxidative stress and neuro-inflammation followed by learning and memory impairment in adolescent male rats. • Ascorbic acid (AA) improved learning and memory impairment. • Vit C decreased serum corticosterone level, brain oxidative stress damage and increased BDNF and neurogenesis. The present research study aimed to investigate the role of Ascorbic acid (AA) on synaptic plasticity, learning, and memory impairment induced by unpredicted chronic mild stress (CUMS) in adolescent male rats. Adolescent male rats were divided into: 1) vehicle, 2) CUMS, 3–5) CUMS plus various doses of AA by oral gavage (CUMS-10/100/400 mg/kg), and 6) AA400 mg/kg by oral gavage. In Morris Water Maze, the time latency decreased, while the time spent in the target quadrant increased in CUMS group treated with AA at the dose of 400 mg/kg. In passive avoidance, the latency of entering into the dark chamber decreased in CUMS group treated with AA (400 mg/kg). In biochemical test results, nitrite and MDA significantly decreased, while thiol content, SOD, and catalase activity in CUMS group that received AA400mg/kg was increased. IL-10, BDNF and Ki67 increased, while TNF-a and AChE activity were decreased in CUMS group treated with AA simultaneously. The results of our study showed that chronic stress during adolescence could cause learning and memory disorders as well as synaptic plasticity. In addition, we showed that AA can prevent this problem by reducing oxidative stress, inflammation, increasing the amount of BDNF, and neurogenesis. [ABSTRACT FROM AUTHOR]

• In preclinical models, fructose induces deficits in spatial and recognition memory. • Female rodents are more resistant to memory impairment induced by fructose. • Neuroinflammation and oxidative stress are short-term underlying mechanisms. • Fructose intake triggers neurogenesis inhibition and LTP decay in the long term. • Clinical data suggest an association between fructose and memory impairment. Fructose consumption has increased over the years, especially in adolescents living in urban areas. Growing evidence indicates that daily fructose consumption leads to some pathological conditions, including memory impairment. This review summarizes relevant data describing cognitive deficits after fructose intake and analyzes the underlying neurobiological mechanisms. Preclinical experiments show sex-related deficits in spatial memory; that is, while males exhibit significant imbalances in spatial processing, females seem unaffected by dietary supplementation with fructose. Recognition memory has also been evaluated; however, only female rodents show a significant decline in the novel object recognition test performance. According to mechanistic evidence, fructose intake induces neuroinflammation, mitochondrial dysfunction, and oxidative stress in the short term. Subsequently, these mechanisms can trigger other long-term effects, such as inhibition of neurogenesis, downregulation of trophic factors and receptors, weakening of synaptic plasticity, and long-term potentiation decay. Integrating all these neurobiological mechanisms will help us understand the cellular and molecular processes that trigger the memory impairment induced by fructose. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) is one of the most prescribed drugs for epilepsy. Extended use of VPA not only induces hepatotoxicity but also impairs the cognitive functions. Metformin has been reported to prevent epileptogenesis and enhance memory. To counter the VPA-induced adverse events, it is hypothesized that combination of sub-therapeutic dose of VPA with metformin may attenuate the toxicity stemming from the therapeutic dose of VPA. Pentylenetetrazole (PTZ)-induced kindling model of epilepsy in mice was used to assess the combined effects of sub-therapeutic dose of VPA (100 mg/kg) and metformin (200 mg/kg). The memory performance was analyzed by passive avoidance test, while alkaline comet assay was used to determine genotoxicity. Histopathological examination and serum biochemical analysis was performed to determine hepatotoxicity. Results showed that combination dose of VPA with metformin reduced seizure scores. VPA (300 mg/kg) administered as a single agent did not enhance memory impairment caused by PTZ, however, combination of sub-therapeutic dose of VPA with metformin enhanced memory function. Furthermore, in alkaline comet assay, combination therapy demonstrated reduced genotoxicity compared to the VPA 300 mg/kg. Histopathological examination of liver and analysis of serum hepatic enzymes revealed that combination therapy (VPA + metformin) reversed the toxicity as seen in case of PTZ or VPA (300 mg/kg) treated animals with no other treatment given. Based on the study data, it is concluded that the combination of sub-therapeutic dose of VPA with metformin might be used for epileptic seizures. This will prevent the hepatotoxicity and enhanced memory functions as compared to the VPA given as a single agent therapy. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is an increasing widespread cause of disability and mortality, typically leading to dementia and memory impairment. Objective: This study aims to investigate the neuroprotective potential of Nigella sativa extract against TBI induced memory impairment in adult albino mice. Methods: Adult male mice were divided into four groups randomly: Control, Nigella sativa extract alone, TBI alone and TBI plus Nigella sativa extract. TBI induction was carried out in mice using a weight dropping method then Nigella sativa extract (10 mg/kg) was administered intraperitoneally for two weeks. Morris water maze and Y-maze tests were used to measure memory improvement ability and Western blot technique was used to analyse the neuroinflammatory and synaptic protein markers. Results: Nigella sativa extract significantly decreased phosphorylated c-Jun N-terminal kinase (p-JNK), Tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) proteins to reduce TBI-induced neuroinflammation accompanied by the restoration of both pre- and post-synaptic protein expression in adult mice model. Furthermore, Nigella sativa extract enhanced both short and long-term spatial memory against TBI in adult mice model. Conclusion: Nigella sativa extract abrogated neuroinflammation mediated memory impairment in TBI mice model. Further research is needed to determine Nigella sativa extract ingredients detail completely and to understand its mechanisms of neuroprotection in reducing memory impairments associated with traumatic brain injury and other neurodegenerative diseases.

Cyclophosphamide (CYL) is a first-line cancer chemotherapeutic agent widely used for the treatment of cancer that has severe toxic effects. The primary mechanism by which CYL induces toxicity through free radical generation. Morinda citrifolia (Noni) fruit juice is an herbal remedy documented to have antioxidant properties. The aim of the current study was to investigate the protective effect of noni against CYL-induced memory impairment in Swiss albino mice. Treatment schedule: Group 1: Normal: Received vehicle; Group 2: CYL treatment: Received CYL (40.0 mg/kg b.w. i.p.) on day one; Group 3: NJ treatment: Received NJ (360 mg/b.w. p.o.) once daily for 14 days. Group 4: DNG treatment: DNG (360 mg/b.w. p.o.) once daily for 14 days, Group 5: NJ + CYL treatment: Received CYL (40.0 mg/kg b.w. i.p.) on day one and after half an hour of received NJ (360 mg/b.w. p.o.) once daily for 14 days. Group 6: DNG + CYL treatment: Received CYL (40.0 mg/kg b.w. i.p.) on day one and after half an hour received DNG (360 mg/b.w. p.o.) once daily for 14 days. Mice were subjected to the Morris water maze (MWM) challenge for two weeks as part of a behavioral study. Short-term memory impairment was observed in the behavioral activity of CYL-treated mice in the MWM test in the 1st week trial, and this effect was reversed in the 2nd week trial in the combination treatment group. The behavioral analysis proved that noni supplementation reduced the risk of memory impairment caused by CYL. Biochemical analysis revealed that CYL markedly increased the levels of AChE and MDA in brain tissue. Similarly, decreases in the levels of antioxidants, i.e., GSH, CAT, SOD and GST, were detected in the brain tissue of the mice exposed to CYL. Qualitative and quantitative examinations of histopathological examination of the mouse hippocampus supported the above findings. The results demonstrated that noni supplement therapy reversed the changes in the MDA, AChE, and antioxidant enzyme levels while improving the behavioral and histological alterations caused by CYL. Long-term hippocampal growth and memory are unaffected, suggesting that CYL is less harmful. According to our research, supplementing with noni in conjunction with CYL may be a helpful treatment strategy for treating memory impairment caused by CYL.

Alzheimer’s disease (AD) is characterized by cognitive impairment, loss of learning and memory, and abnormal behaviors. Scopolamine (SCOP) is a non-selective antagonist of muscarinic acetylcholine receptors that exhibits the behavioral and molecular hallmarks of AD. Vanillic acid (VA), a phenolic compound, is obtained from the roots of a traditional plant called Angelica sinensis, and has several pharmacologic effects, including antimicrobial, anti-inflammatory, anti-angiogenic, anti-metastatic, and antioxidant properties. Nevertheless, VA’s neuroprotective potential associated with the memory has not been thoroughly investigated. Therefore, this study investigated whether VA treatment has an ameliorative effect on the learning and memory impairment induced by SCOP in rats. Behavioral experiments were utilized to assess the learning and memory performance associated with the hippocampus. Using western blotting analysis and assay kits, the neuronal damage, oxidative stress, and acetylcholinesterase activity responses of hippocampus were evaluated. Additionally, the measurement of long-term potentiation was used to determine the function of synaptic plasticity in organotypic hippocampal slice cultures. In addition, the synaptic vesicles’ density and the length and width of the postsynaptic density were evaluated using electron microscopy. Consequently, the behavioral, biochemical, electrophysiological, and ultrastructural analyses revealed that VA treatment prevents learning and memory impairments caused by SCOP in rats. The study’s findings suggest that VA has a neuroprotective effect on SCOP-induced learning and memory impairment linked to the hippocampal cholinergic system, oxidative damage, and synaptic plasticity. Therefore, VA may be a prospective therapeutic agent for treating AD.

Abstract Background The pathogenesis of memory impairment, a common complication of chronic neuropathic pain (CNP), has not been fully elucidated. Schwann cell (SC)-derived extracellular vesicles (EVs) contribute to remote organ injury. Here, we showed that SC-EVs may mediate pathological communication between SCs and hippocampal neurons in the context of CNP. Methods We used an adeno-associated virus harboring the SC-specific promoter Mpz and expressing the CD63-GFP gene to track SC-EVs transport. microRNA (miRNA) expression profiles of EVs and gain-of-function and loss-of-function regulatory experiments revealed that miR-142-5p was the main cargo of SC-EVs. Next, luciferase reporter gene and phenotyping experiments confirmed the direct targets of miR-142-5p. Results The contents and granule sizes of plasma EVs were significantly greater in rats with chronic sciatic nerve constriction injury (CCI)than in sham rats. Administration of the EV biogenesis inhibitor GW4869 ameliorated memory impairment in CCI rats and reversed CCI-associated dendritic spine damage. Notably, during CCI stress, SC-EVs could be transferred into the brain through the circulation and accumulate in the hippocampal CA1-CA3 regions. miR-142-5p was the main cargo wrapped in SC-EVs and mediated the development of CCI-associated memory impairment. Furthermore, α-actinin-4 (ACTN4), ELAV-like protein 4 (ELAVL4) and ubiquitin-specific peptidase 9 X-linked (USP9X) were demonstrated to be important downstream target genes for miR-142-5p-mediated regulation of dendritic spine damage in hippocampal neurons from CCI rats. Conclusion Together, these findings suggest that SCs-EVs and/or their cargo miR-142-5p may be potential therapeutic targets for memory impairment associated with CNP.

Abstract Background Alzheimer’s disease (AD) and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) are debilitating neurodegenerative diseases for which there are currently no cures. Familial cases with known genetic causes make up less than 10% of these diseases, and little is known about the underlying mechanisms that contribute to sporadic disease. Accordingly, it is important to expand investigations into possible pathways that may contribute to disease pathophysiology. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a membrane-bound enzyme that acts at the cell surface to cleave the glycosylphosphatidylinositol (GPI)-anchor that tethers distinct proteins to the membrane. GDE2 abnormally accumulates in intracellular compartments in the brain of patients with AD, ALS, and ALS/FTD, indicative of GDE2 dysfunction. Mice lacking GDE2 (Gde2KO) show neurodegenerative changes such as neuronal loss, reduced synaptic proteins and synapse loss, and increased Aβ deposition, raising the possibility that GDE2 disruption in disease might contribute to disease pathophysiology. However, the effect of GDE2 loss on behavioral function and learning/memory has not been characterized. Results Here, we show that GDE2 is expressed throughout the adult mouse brain in areas including the cortex, hippocampus, habenula, thalamus, and amygdala. Gde2KO and WT mice were tested in a set of behavioral tasks between 7 and 16 months of age. Compared to WT, Gde2KO mice display moderate hyperactivity that becomes more pronounced with age across a variety of behavioral tests assessing novelty-induced exploratory activity. Additionally, Gde2KO mice show reduced startle response, with females showing additional defects in prepulse inhibition. No changes in anxiety-associated behaviors were found, but Gde2KOs show reduced sociability. Notably, aged Gde2KO mice demonstrate impaired short/long-term spatial memory and cued fear memory/secondary contextual fear acquisition. Conclusions Taken together, these observations suggest that loss of GDE2 leads to behavioral deficits, some of which are seen in neurodegenerative disease models, implying that loss of GDE2 may be an important contributor to phenotypes associated with neurodegeneration.

Background and Aim: Huntington's disease is a chronic hereditary disorder that causes cognitive and movement defects in affected individuals by progressive destruction of neurons in the cerebral cortex, striatum and the hippocampus. Studies have shown that increased activity of cyclin-dependent kinase-5 (CDK5) plays an important role in the pathogenesis and occurrence of memory impairment in Huntington's disease. Recently, alpha-pinene has been reported to improve learning and memory performance in Alzheimer's and Parkinson's models. Therefore, the aim of this study was to investigate the effect of alpha-pinene on passive avoidance memory and CDK5 gene expression in Huntington's animal model induced by 3-nitro-propionic acid (3-NP). Materials and Methods: In this study, 40 male rats were randomly divided into 5 groups: sham, 3-NP (10 mg/kg),and 3 other groups receiving 3-NP (10 mg/kg) + alpha-pinene at doses of 1, 5 and 10 mg/kg (for 3 weeks,via intraperitoneal injection). Passive avoidance memory was assessed through the shuttle box device. Then, the expression level of CDK5 gene was measured by RT-qPCR method in brain cortex and hippocampus. Results: 3-NP injection caused memory impairment by decreasing step through latency (STL). Alpha-pinene at all three doses improved passive avoidance memory performance. Also, 3-NP injection caused a significant increase in CDK5 gene expression level in the brain cortex and hippocampus compared to that in the sham group. The groups which received alpha-pinene at doses of 5 and 10 mg/kg in brain cortex and 1 mg/kg in hippocampus showed decreased expression level of this gene compared to the group that received 3-NP. Conclusion: The results of this study showed that alpha-pinene improves passive avoidance memory performance probably by reducing the CDK5 gene expression level in Huntington's animal model induced by 3-NP.

ABSTRACTGut – brain communications disorders in irritable bowel syndrome (IBS) are associated with intestinal microbiota composition, increased gut permeability, and psychosocial disturbances. Symptoms of IBS are difficult to medicate, and hence much research is being made into alternative approaches. This study assesses the potential of a treatment with pasteurized Akkermansia muciniphila for alleviating IBS-like symptoms in two mouse models of IBS with different etiologies. Two clinically relevant animal models were used to mimic IBS-like symptoms in C57BL6/J mice: the neonatal maternal separation (NMS) paradigm and the Citrobacter rodentium infection model. In both models, gut permeability, colonic sensitivity, fecal microbiota composition and colonic IL-22 expression were evaluated. The cognitive performance and emotional state of the animals were also assessed by several tests in the C. rodentium infection model. The neuromodulation ability of pasteurized A. muciniphila was assessed on primary neuronal cells from mice dorsal root ganglia using a ratiometric calcium imaging approach. The administration of pasteurized A. muciniphila significantly reduced colonic hypersensitivity in both IBS mouse models, accompanied by a reinforcement of the intestinal barrier function. Beneficial effects of pasteurized A. muciniphila treatment have also been observed on anxiety-like behavior and memory defects in the C. rodentium infection model. Finally, a neuroinhibitory effect exerted by pasteurized A. muciniphila was observed on neuronal cells stimulated with two algogenic substances such as capsaicin and inflammatory soup. Our findings demonstrate novel anti-hyperalgesic and neuroinhibitory properties of pasteurized A. muciniphila, which therefore may have beneficial effects in relieving pain and anxiety in subjects with IBS.

Background: The pathogenesis of memory impairment, a common complication of chronic neuropathic pain (CNP), has not been fully elucidated. Schwann cell (SC)-derived extracellular vesicles (EVs) contribute to remote organ injury. Here, we showed that SC-EVs may mediate pathological communication between SCs and hippocampal neurons in the context of CNP. Methods: We used an adeno-associated virus harboring the SC-specific promoter Mpz and expressing the CD63-GFP gene to track SC-EVs transport. microRNA (miRNA) expression profiles of EVs and gain-of-function and loss-of-function regulatory experiments revealed that miR-142-5p was the main cargo of SC-EVs. Next, luciferase reporter gene and phenotyping experiments confirmed the direct targets of miR-142-5p. Results: The contents and granule sizes of plasma EVs were significantly greater in rats with chronic sciatic nerve constriction injury (CCI)than in sham rats. Administration of the EV biogenesis inhibitor GW4869 ameliorated memory impairment in CCI rats and reversed CCI-associated dendritic spine damage. Notably, during CCI stress, SC-EVs could be transferred into the brain through the circulation and accumulate in the hippocampal CA1-CA3 regions. miR-142-5p was the main cargo wrapped in SC-EVs and mediated the development of CCI-associated memory impairment. Furthermore, α-actinin-4 (ACTN4), ELAV-like protein 4 (ELAVL4) and ubiquitin-specific peptidase 9 X-linked (USP9X) were demonstrated to be important downstream target genes for miR-142-5p-mediated regulation of dendritic spine damage in hippocampal neurons from CCI rats. Conclusion: Together, these findings suggest that SCs-EVs and/or their cargo miR-142-5p may be potential therapeutic targets for memory impairment associated with CNP. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) are debilitating neurodegenerative diseases for which there are currently no cures. Familial cases with known genetic causes make up less than 10% of these diseases, and little is known about the underlying mechanisms that contribute to sporadic disease. Accordingly, it is important to expand investigations into possible pathways that may contribute to disease pathophysiology. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a membrane-bound enzyme that acts at the cell surface to cleave the glycosylphosphatidylinositol (GPI)-anchor that tethers distinct proteins to the membrane. GDE2 abnormally accumulates in intracellular compartments in the brain of patients with AD, ALS, and ALS/FTD, indicative of GDE2 dysfunction. Mice lacking GDE2 (Gde2KO) show neurodegenerative changes such as neuronal loss, reduced synaptic proteins and synapse loss, and increased Aβ deposition, raising the possibility that GDE2 disruption in disease might contribute to disease pathophysiology. However, the effect of GDE2 loss on behavioral function and learning/memory has not been characterized. Results: Here, we show that GDE2 is expressed throughout the adult mouse brain in areas including the cortex, hippocampus, habenula, thalamus, and amygdala. Gde2KO and WT mice were tested in a set of behavioral tasks between 7 and 16 months of age. Compared to WT, Gde2KO mice display moderate hyperactivity that becomes more pronounced with age across a variety of behavioral tests assessing novelty-induced exploratory activity. Additionally, Gde2KO mice show reduced startle response, with females showing additional defects in prepulse inhibition. No changes in anxiety-associated behaviors were found, but Gde2KOs show reduced sociability. Notably, aged Gde2KO mice demonstrate impaired short/long-term spatial memory and cued fear memory/secondary contextual fear acquisition. Conclusions: Taken together, these observations suggest that loss of GDE2 leads to behavioral deficits, some of which are seen in neurodegenerative disease models, implying that loss of GDE2 may be an important contributor to phenotypes associated with neurodegeneration. [ABSTRACT FROM AUTHOR]

Many people around the world suffer from neurodegenerative diseases associated with cognitive impairment. As life expectancy increases, this number is steadily rising. Therefore, it is extremely important to search for new treatment strategies and to discover new substances with potential neuroprotective and/or cognition-enhancing effects. This study focuses on investigating the potential of astragaloside IV (AIV), a triterpenoid saponin with proven acetylcholinesterase (AChE)-inhibiting activity naturally occurring in the root of Astragalus mongholicus, to attenuate memory impairment. Scopolamine (SCOP), an antagonist of muscarinic cholinergic receptors, and lipopolysaccharide (LPS), a trigger of neuroinflammation, were used to impair memory processes in the passive avoidance (PA) test in mice. This memory impairment in SCOP-treated mice was attenuated by prior intraperitoneal (ip) administration of AIV at a dose of 25 mg/kg. The attenuation of memory impairment by LPS was not observed. It can therefore be assumed that AIV does not reverse memory impairment by anti-inflammatory mechanisms, although this needs to be further verified. All doses of AIV tested did not affect baseline locomotor activity in mice. In the post mortem analysis by mass spectrometry of the body tissue of the mice, the highest content of AIV was found in the kidneys, then in the spleen and liver, and the lowest in the brain. [ABSTRACT FROM AUTHOR]

Sporadic or late-onset Alzheimer's disease (LOAD) accounts for more than 95% of Alzheimer's disease (AD) cases without any family history. Although genome-wide association studies have identified associated risk genes and loci for LOAD, numerous studies suggest that many adverse environmental factors, such as social isolation, are associated with an increased risk of dementia. However, the underlying mechanisms of social isolation in AD progression remain elusive. In the current study, we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD mice. We also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus (DG)-enriched miRNAs, which simultaneously target reticulon 3 (RTN3), an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons (MFBs) by recruiting multiple mitochondrial and vesicle-related proteins. Interestingly, the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation, which, in turn, further elevates RTN3 and forms a vicious cycle. Finally, using an artificial intelligence-assisted molecular docking approach, we determined that senktide, a selective agonist of neurokinin3 receptors (NK3R), could reduce the binding of RTN3 with its partners. Moreover, application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD mice. Taken together, our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD. [ABSTRACT FROM AUTHOR]

• ICV inoculation of C. acnes causes memory impairment in Wistar rats. • C. acnes promotes the generation of Aβ deposits in the rat hippocampus. • C. acnes actives the innate immune system to increase neuroinflammation through TLR2/NF-κB/NLRP3 signaling. • C. acnes induces gliosis and oxidation damage through increasing MDA levels and decreasing SOD activity. • C. acnes induces cell death through apoptosis and, or pyroptosis. The infection hypothesis is a new causative explanation for Alzheimer's disease (AD). In recent decades, various species of bacterial pathogens have been distinguished in the autopsy of Alzheimer's patients; however, the mechanism of bacterial contribution to AD pathology is still unknown. To explore the hypothesis, Cutibacterium acnes (C. acnes) was selected, and effects of its intracerebroventricular (ICV) inoculation in rats was evaluated. The results revealed that C. acnes causes memory impairment, which might be a consequence of upregulated Amyloid β (Aβ) deposits in the hippocampus; Aβ aggregates are co-localized with C. acnes colonies. The key point of our hypothesis is that the activation of the innate immune system by C. acnes through the TLR2/NF-κB/NLRP3 signaling pathway, eventually leads to increased neuroinflammation, which might be resulted from microgliosis and astrogliosis. Neuroinflammation increases oxidative stress and cell apoptosis. Overall, the obtained results of this study support our hypothesis that brain exposure to C. acnes prompted neuroinflammation with similar AD-like pathology. [ABSTRACT FROM AUTHOR]

We evaluated the role and mechanism of acteoside in the regulation of memory impairment induced by chronic unpredictable mild stress (CUMS). CUMS was used to induce depression in rats and the successful establishment of CUMS model were verified by forced swimming test and sucrose preference test. The Y-maze test and novel object recognition test assessed memory functions. The structural changes in the cortex and hippocampus were observed by hematoxylin and eosin (HE) staining. Immunofluorescence staining and western blotting determined the protein levels. Y-maze test and novel object recognition test showed that there was memory performance impairment in rats of CUMS group, which was improved by the acteoside treatment. HE staining showed that CUMS exposure damaged the structure in the cortex and hippocampus, while the acteoside treatment alleviated the structural changes. Compared with the control group, the levels of BNDF and CREB in the cortex and hippocampus of the CUMS group were significantly decreased. Acteoside significantly reversed the expressions of these proteins in CUMS rats. Meanwhile, compared with the control group, the levels of p-mTOR and pP70S6K in the cortex and hippocampus of the CUMS group were significantly increased, and these changes were significantly reversed by acteoside. Nevertheless, the effect of acteoside on mTOR signaling was markedly blocked by rapamycin, a specific inhibitor of mTOR signaling. Acteoside can attenuate memory impairment and ameliorate neuronal damage and synaptic plasticity in depression rats probably via inhibiting the mTOR signaling pathway. Acteoside may serve as a novel reagent for the prevention of depression. [ABSTRACT FROM AUTHOR]

Objective To explore the correlation between abnormal thalamic functional connectivity (FC) and memory loss in maintenance hemodialysis patients with end-stage renal disease (ESRD). Methods An auditory verbal learning test (AVLT-H) was conducted on 22 patients with ESRD and 28 age-, sex-, and education-matched healthy controls (HC) to evaluate memory function. After that, resting-state functional magnetic resonance imaging (rs-fMRI) data were gathered, and a whole-brain FC analysis centered on the thalamus was executed to discern variations in thalamic FC between the two groups. Finally, Pearson and Spearman correlation analyses were carried out. Results Compared to the HC group, the ESRD group exhibited notably lower scores in IR-S (P=0.002), SR-S (P<0.001), and LR-S (P=0.005). Concurrently, the ESRD group demonstrated diminished FC of the right thalamus with the left superior frontal gyrus, the left parietal lobule, the right suproccipital gyrus, the right anterior cuneus, and the right middle frontal gyrus (P<0.05, TFCE correction). Additionally, reduced FC were observed between the left thalamus and the left gyrus rectus, the left parietal lobule, and the right parietal lobule in the ESRD group (P<0.05, TFCE correction). Moreover, the FC values between the left thalamus and the left gyrus rectus in the ESRD group displayed significant negative correlations with IR-S (r=-0.499), SR-S (r=-0.458), and LR-S (r=-0.455) (all P<0.05). Conclusion Memory impairment is evident in ESRD patients undergoing maintenance hemodialysis, and it appears to be intricately linked to anomalous FC within the left thalamus and the left gyrus rectus. These findings offer potential imaging markers for monitoring memory dysfunction in individuals with ESRD. [ABSTRACT FROM AUTHOR]

Fermented mixed grain (FG) has beneficial anti-cancer, antioxidant, and anti-inflammatory effects. In this study, we investigated the effects of FG on gut inflammation, brain dysfunction, and anxiety/depression-like behavior induced by unpredictable chronic mild stress (UCMS) in mice. Mice were administered mixed grain or FG for 3 weeks and were then exposed to UCMS for 4 weeks. FG administration ameliorated stress-induced anxiety/despair-like behavior. FG administration also prevented UCMS-induced memory impairment. Additionally, the mRNA levels of 5-HTR1A and IL-6 were restored to normal levels in the brains of FG-administered mice. FG administration also inhibited intestinal damage in stressed mice compared with that in the UCMS (without FG) group. These results suggest that FG can alleviate stress-induced intestinal damage, brain dysfunction, and cognitive impairment. [ABSTRACT FROM AUTHOR]

Sleep deprivation (SD) has reached epidemic proportions worldwide and negatively affects people of all ages. Cognitive impairment induced by SD involves neuroinflammation and mitochondrial dysfunction, but the underlying mechanisms are largely unknown. Urolithin A (UA) is a natural compound that can reduce neuroinflammation and improve mitochondrial health, but its therapeutic effects in a SD model have not yet been studied. Young (3-months old) and aged (12-months old) mice were sleep deprived for 24 h, and UA (2.5 mg/kg or 10 mg/kg) was injected intraperitoneally for 7 consecutive days before the SD period. Immunofluorescent staining, western blotting, and RT-PCR were employed to evaluate levels of proteins involved in neuroinflammation and mitochondrial function. Transmission electron microscope and Golgi-Cox staining were used to evaluate mitochondrial and neuronal morphology, respectively. Finally, contextual fear conditioning and the Morris water maze test were conducted to assess hippocampal learning and memory. In the hippocampus of young (3 months-old) and aged (12 months-old) mice subjected to 24 h SD, pretreatment with UA prevented the activation of microglia and astrocytes, NF-κB-NLRP3 signaling and IL-1β, IL6, TNF-α cytokine production, thus ameliorating neuroinflammation. Furthermore, UA also attenuated SD-induced mitochondrial dysfunction, normalized autophagy and mitophagy and protected hippocampal neuronal morphology. Finally, UA prevented SD-induced hippocampal memory impairment. Cumulatively, the results show that UA imparts cognitive protection by reducing neuroinflammation and enhancing mitochondrial function in SD mice. This suggests that UA shows promise as a therapeutic for the treatment of SD-induced neurological disorders. [ABSTRACT FROM AUTHOR]

Introduction: Prior MRI studies have shown that patients with subcortical ischemic vascular disease (SIVD) exhibited white matter damage, gray matter atrophy and memory impairment, but the specific characteristics and interrelationships of these abnormal changes have not been fully elucidated. Materials and methods: We collected the MRI data and memory scores from 29 SIVD patients with cognitive impairment (SIVD-CI), 29 SIVD patients with cognitive unimpaired (SIVD-CU) and 32 normal controls (NC). Subsequently, the thicknesses and volumes of the gray matter regions that are closely related to memory function were automatically assessed using FreeSurfer software. Then, the volume, fractional anisotropy (FA), mean diffusivity (MD), amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values of white matter hyperintensity (WMH) region and normal-appearing white matter (NAWM) were obtained using SPM, DPARSF, and FSL software. Finally, the analysis of covariance, spearman correlation and mediation analysis were used to analyze data. Results: Compared with NC group, patients in SIVD-CI and SIVD-CU groups showed significantly abnormal volume, FA, MD, ALFF, and ReHo values of WMH region and NAWM, as well as significantly decreased volume and thickness values of gray matter regions, mainly including thalamus, middle temporal gyrus and hippocampal subfields such as cornu ammonis (CA) 1. These abnormal changes were significantly correlated with decreased visual, auditory and working memory scores. Compared with the SIVD-CU group, the significant reductions of the left CA2/3, right amygdala, right parasubiculum and NAWM volumes and the significant increases of the MD values in the WMH region and NAWM were found in the SIVD-CI group. And the increased MD values were significantly related to working memory scores. Moreover, the decreased CA1 and thalamus volumes mediated the correlations between the abnormal microstructure indicators in WMH region and the decreased memory scores in the SIVD-CI group. Conclusion: Patients with SIVD had structural and functional damages in both WMH and NAWM, along with specific gray matter atrophy, which were closely related to memory impairment, especially CA1 atrophy and thalamic atrophy. More importantly, the volumes of some temporomesial regions and the MD values of WMH regions and NAWM may be potentially helpful neuroimaging indicators for distinguishing between SIVD-CI and SIVD-CU patients. [ABSTRACT FROM AUTHOR]

Background: The FACEmemory® online platform comprises a complex memory test and sociodemographic, medical, and family questions. This is the first study of a completely self-administered memory test with voice recognition, pre-tested in a memory clinic, sensitive to Alzheimer's disease, using information and communication technologies, and offered freely worldwide. Objective: To investigate the demographic and clinical variables associated with the total FACEmemory score, and to identify distinct patterns of memory performance on FACEmemory. Methods: Data from the first 3,000 subjects who completed the FACEmemory test were analyzed. Descriptive analyses were applied to demographic, FACEmemory, and medical and family variables; t-test and chi-square analyses were used to compare participants with preserved versus impaired performance on FACEmemory (cut-off = 32); multiple linear regression was used to identify variables that modulate FACEmemory performance; and machine learning techniques were applied to identify different memory patterns. Results: Participants had a mean age of 50.57 years and 13.65 years of schooling; 64.07% were women, and 82.10% reported memory complaints with worries. The group with impaired FACEmemory performance (20.40%) was older, had less schooling, and had a higher prevalence of hypertension, diabetes, dyslipidemia, and family history of neurodegenerative disease than the group with preserved performance. Age, schooling, sex, country, and completion of the medical and family history questionnaire were associated with the FACEmemory score. Finally, machine learning techniques identified four patterns of FACEmemory performance: normal, dysexecutive, storage, and completely impaired. Conclusions: FACEmemory is a promising tool for assessing memory in people with subjective memory complaints and for raising awareness about cognitive decline in the community. [ABSTRACT FROM AUTHOR]

Background and Objective: Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra‐motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and neuropsychological assessments of the hippocampal and parahippocampal regions in patients with ALS. Methods: A systematic review was conducted in the Scopus and PubMed databases for studies published between January 2000 and July 2023. The inclusion criteria were (1) MRI studies to assess hippocampal and parahippocampal regions in ALS patients, and (2) studies reporting neuropsychological data in patients with ALS. Results: A total of 46 studies were included. Structural MRI revealed hippocampal atrophy, especially in ALS‐FTD, involving specific subregions (CA1, dentate gyrus). Disease progression and genetic factors impacted atrophy patterns. Diffusion tensor imaging (DTI) showed increased mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and decreased fractional anisotropy (FA) in the hippocampal tracts and adjacent regions, indicating loss of neuronal and white matter integrity. Functional MRI (fMRI) revealed reduced functional connectivity (FC) between the hippocampus, parahippocampus, and other regions, suggesting disrupted networks. Perfusion MRI showed hypoperfusion in parahippocampal gyri. Magnetic resonance spectroscopy (MRS) found changes in the hippocampus, indicating neuronal loss. Neuropsychological tests showed associations between poorer memory and hippocampal atrophy or connectivity changes. CA1‐2, dentate gyrus, and fimbria atrophy were correlated with worse memory. Conclusions: The hippocampus and the connected regions are involved in ALS. Hippocampal atrophy disrupted connectivity and metabolite changes correlate with cognitive and functional decline. Specific subregions can be particularly affected. The hippocampus is a potential biomarker for disease monitoring and prognosis. [ABSTRACT FROM AUTHOR]

Aims: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. AD pathology involves protein acetylation. Previous studies have mainly focused on histone acetylation in AD, however, the roles of nonhistone acetylation in AD are less explored. Methods: The protein acetylation and expression levels were detected by western blotting and co‐immunoprecipitation. The stoichiometry of acetylation was measured by home‐made and site‐specific antibodies against acetylated‐CaM (Ac‐CaM) at K22, K95, and K116. Hippocampus‐dependent learning and memory were evaluated by using the Morris water maze, novel object recognition, and contextual fear conditioning tests. Results: We showed that calmodulin (CaM) acetylation is reduced in plasma of AD patients and mice. CaM acetylation and its target Ca2+/CaM‐dependent kinase II α (CaMKIIα) activity were severely impaired in AD mouse brain. The stoichiometry showed that Ac‐K22, K95‐CaM acetylation were decreased in AD patients and mice. Moreover, we screened and identified that lysine deacetylase 9 (HDAC9) was the main deacetylase for CaM. In addition, HDAC9 inhibition increased CaM acetylation and CaMKIIα activity, and hippocampus‐dependent memory in AD mice. Conclusions: HDAC9‐mediated CaM deacetylation induces memory impairment in AD, HDAC9, or CaM acetylation may become potential therapeutic targets for AD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Recent research suggests that butin may also exert neuroprotective effects. However, its influence on cognitive performance and, specifically, its potential to mitigate scopolamine-induced memory impairment remains unexplored. The aim of the study is to investigate the effects of butin on the cognitive and behavioral performance of rats with scopolamine-induced memory impairment. MATERIALS AND METHODS: Scopolamine-injected memory-impediment model in rats was used to determine the efficacy of butin in higher and lower doses (10 and 20 mg/kg) for 14 days. Y-maze, along with Morris water, was used to assess the ability to recall spatial and working information. Biochemistry-related functions such as acetylcholinesterase, choline acetyltransferase, superoxide dismutase, glutathione transferase, malonaldehyde, catalase, nitric oxide and neurotransmitters levels were estimated as indicators of free radical damage. Furthermore, we evaluated neuro-inflammatory responses by assessing tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and caspase-3 immuno-reactive proteins. RESULTS: When assessed through behavioral paradigms, the butin-treated group enhanced the spatial and working memory of rodents. Scopolamine caused a substantial alteration in biochemical-related parameters, neuronal enzymatic, inflammation responses and apoptosis markers prominently restored by butin. CONCLUSIONS: This study concludes that butin protects scopolamine-injected rats from behavioral impairments and neuronal damage by reducing apoptosis and neuroinflammation. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced cognitive impairment (CICI) is one of the major adverse effects of antineoplastic drugs, which decrease the quality of life in cancer survivors. Extensive experimental and clinical research suggests that chemotherapeutic drugs generate an enormous amount of reactive oxygen species (ROS), contributing to oxidative stress, neuroinflammation, blood-brain barrier (BBB) disruption, and neuronal death, eventually leading to CICI. Despite the progress in exploring different pathological mechanisms of CICI, effective treatment to prevent CICI progression has not been developed yet. Nrf2 is the principal transcription factor that regulates cellular redox balance and inflammation-related gene expression. Emerging evidence suggests that upregulation of Nrf2 and its target genes could suppress oxidative stress, and neuroinflammation, restore BBB integrity, and increase neurogenesis. This review discusses the role of Nrf2 in CICI, how it responds to oxidative stress, inflammation, neurotoxicity, and potential Nrf2 activators that could be used to enhance Nrf2 activation in CICI. [ABSTRACT FROM AUTHOR]