Search

Acoel flatworms have played a relevant role in classical (and current) discussions on the evolutionary origin of bilaterian animals. This is mostly derived from the apparent simplicity of their body architectures. This tenet has been challenged over the last couple of decades, mostly because detailed studies of their morphology and the introduction of multiple genomic technologies have unveiled a complexity of cell types, tissular arrangements and patterning mechanisms that were hidden below this superficial simplicity. One tissue that has received a particular attention has been the nervous system (NS). The combination of ultrastructural and single cell methodologies has revealed unique cellular diversity and developmental trajectories for most of their neurons and associated sensory systems. Moreover, the great diversity in NS architectures shown by different acoels offers us with a unique group of animals where to study key aspects of neurogenesis and diversification od neural systems over evolutionary time.In this review we revisit some recent developments in the characterization of the acoel nervous system structure and the regulatory mechanisms that contribute to their embryological development. We end up by suggesting some promising avenues to better understand how this tissue is organized in its finest cellular details and how to achieve a deeper knowledge of the functional roles that genes and gene networks play in its construction.

The referent control theory (RCT) for action and perception is an advanced formulation of the equilibrium-point hypothesis. The RCT suggests that rather than directly specifying the desired motor outcome, the nervous system controls action and perception indirectly by setting the values of parameters of physical and physiological laws. This is done independently of values of kinematic and kinetic variables including electromyographic patterns describing the motor outcome. One such parameter-the threshold muscle length, λ, at which motoneurons of a given muscle begin to be recruited, has been identified experimentally. In RCT, a similar parameter. the referent arm position, R, has been defined for multiple ann muscles as the threshold arm position at which arm muscles can be quiescent but activated depending on the deftection of the actual ann position, Q, from R. Changes in R result in reciprocal changes in the activity of opposing muscle groups. We advanced the explanatory power of RCT by combining the usual biomechanical descriptions of motor actions with the identification of the timing of R underlying arm movements made with reversals in three directions and to three different extents. We found that in all movements, periods of minimization of the activity of multiple muscles could be identified at ~61%-86% of the reaching extent in each direction. These electromyographic minimization periods reftect the spatial coordinates at which the R and Q overlap during the production of movements with reversals. The findings support the concept of the production of arm movement by shifting R. [ABSTRACT FROM AUTHOR]

• Cre recombinase targeted to noradrenergic neurons via CRISPR-Cas9. • High specificity of Cre expression validated in locus coeruleus. • New transgenic rat model facilitates detailed neurobehavioral studies. Noradrenergic neurons play a crucial role in the functioning of the nervous system. They formed compact small clusters in the central nervous system. To target noradrenergic neurons in combination with viral tracing and achieve cell-type specific functional manipulation using chemogenetic or optogenetic tools, new transgenic animal lines are needed, especially rat models for their advantages in large body size with facilitating easy operation, physiological parameter monitoring, and accommodating complex behavioral and cognitive studies. In this study, we successfully generated a transgenic rat strain capable of expressing Cre recombinase under the control of the dopamine beta-hydroxylase (DBH) gene promoter using the CRISPR-Cas9 system. Our validation process included co-immunostaining with Cre and DBH antibodies, confirming the specific expression of Cre recombinase. Furthermore, stereotaxic injection of a fluorescence-labeled AAV-DIO virus illustrated the precise Cre-loxP-mediated recombination activity in noradrenergic neurons within the locus coeruleus (LC). Through crossbreeding with the LSL-fluorescence reporter rat line, DBH-Cre rats proved instrumental in delineating the position and structure of noradrenergic neuron clusters A1, A2, A6 (LC), and A7 in rats. Additionally, our specific activation of the LC noradrenergic neurons showed effective behavioral readout using chemogenetics of this rat line. Our results underscore the effectiveness and specificity of Cre recombinase in noradrenergic neurons, serving as a robust tool for cell-type specific targeting of small-sized noradrenergic nuclei. This approach enhances our understanding of their anatomical, physiological, and pathological roles, contributing to a more profound comprehension of noradrenergic neuron function in the nervous system. [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence (AI) has the potential to enhance surgical practice by predicting anatomical structures within the surgical field, thereby supporting surgeons' experiences and cognitive skills. Preserving and utilising nerves as critical guiding structures is paramount in rectal cancer surgery. Hence, we developed a deep learning model based on U-Net to automatically segment nerves. Methods: The model performance was evaluated using 60 randomly selected frames, and the Dice and Intersection over Union (IoU) scores were quantitatively assessed by comparing them with ground truth data. Additionally, a questionnaire was administered to five colorectal surgeons to gauge the extent of underdetection, overdetection, and the practical utility of the model in rectal cancer surgery. Furthermore, we conducted an educational assessment of non-colorectal surgeons, trainees, physicians, and medical students. We evaluated their ability to recognise nerves in mesorectal dissection scenes, scored them on a 12-point scale, and examined the score changes before and after exposure to the AI analysis videos. Results: The mean Dice and IoU scores for the 60 test frames were 0.442 (range 0.0465–0.639) and 0.292 (range 0.0238–0.469), respectively. The colorectal surgeons revealed an under-detection score of 0.80 (± 0.47), an over-detection score of 0.58 (± 0.41), and a usefulness evaluation score of 3.38 (± 0.43). The nerve recognition scores of non-colorectal surgeons, rotating residents, and medical students significantly improved by simply watching the AI nerve recognition videos for 1 min. Notably, medical students showed a more substantial increase in nerve recognition scores when exposed to AI nerve analysis videos than when exposed to traditional lectures on nerves. Conclusions: In laparoscopic and robot-assisted rectal cancer surgeries, the AI-based nerve recognition model achieved satisfactory recognition levels for expert surgeons and demonstrated effectiveness in educating junior surgeons and medical students on nerve recognition. [ABSTRACT FROM AUTHOR]

Arsenic (As) is globally detected in drinking water and food products at levels repeatedly surpassing regulatory thresholds. Several neurological and mental health risks linked to arsenic exposure are proposed; however, the nature of these effects and their association with the chemical forms of arsenic are not fully understood. Gaining a clear understanding of the etiologies and characteristics of these effects is crucial, particularly in association with developmental exposures where the nervous system is most vulnerable. In this study, we investigated the effects of early developmental exposure (6- to 120-h postfertilization [hpf]) of larval zebrafish to environmentally relevant concentrations of arsenic species—trivalent/pentavalent, inorganic/organic forms—on developmental, behavioral, and molecular endpoints to determine their effect on stress response and their potential association with stress-related disorders. At 120 hpf, the developing larvae were assessed for a battery of endpoints including survival, developmental malformities, background activity, and behavioral responses to acute visual and acoustic stimuli. Pooled larval samples were analyzed for alterations in the transcript levels of genes associated with developmental neurotoxicity and stress-related disorders. Developmental exposures at target concentrations did not significantly alter survival, overall development, or background activity, and had minor effects on developmental morphology. Sodium arsenate and monomethylarsonic acid exaggerated the behavioral responses of larval zebrafish, whereas sodium arsenite depressed them. Sodium arsenate induced significant effects on molecular biomarkers. This study highlights the effects of developmental exposure to arsenicals on the behavioral stress response, the role chemical formulation plays in exerting toxicological effects, and the possible association with stress-related disorders. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between neuropsychiatric systemic lupus erythematosus (NPSLE) and SLICC/ACR damage index (SDI) items, especially non-neuropsychiatric items. Methods: Baseline data from five phase III trials (BLISS-52, BLISS-76, BLISS-SC, BLISS-NEA, EMBRACE) were analysed. NPSLE involvement was defined as NP BILAG A/B/C/D (n = 272); NP BILAG E denoted non-neuropsychiatric SLE (n = 3273). We employed multivariable logistic regression analysis adjusting for age, sex, disease duration, and ethnicity. Results: The median (IQR) and mean ± SD SDI scores were 0 (0–1) and 0.62 ± 1.09. Compared with the non-neuropsychiatric SLE group, NPSLE patients were more likely to develop damage (adjusted (a)OR = 2.86; 95% CI = 2.28–3.59). This held true also after suppression of the NP SDI items (aOR = 1.70; 95% CI = 1.36–2.12). Beyond the neuropsychiatric domain, NPSLE was associated with damage in the cardiovascular (aOR = 2.63; 95% CI = 1.75–3.95), musculoskeletal (aOR = 1.90; 95% CI = 1.43–2.52), and skin (aOR = 1.54; 95% CI = 1.06–2.22) SDI domains. Dissecting domains into items, NPSLE was associated with coronary artery disease (aOR = 3.08; 95% CI = 1.44–6.58), myocardial infraction (aOR = 3.11; 95% CI = 1.54–6.27), muscle atrophy (aOR = 3.34; 2.16–5.16), scarring alopecia (aOR = 1.79; 95% CI = 1.19–2.70), bowel infarction (aOR = 1.98; 95% CI = 1.20–3.26), retinopathy (aOR = 2.23; 95% CI = 1.15–4.32), and premature gonadal failure (aOR = 2.10; 95% CI = 1.11–3.90). Conclusion: The intricate association between NPSLE and damage accrual extends beyond the nervous system to also comprise the musculoskeletal, skin, and cardiovascular organ systems. [ABSTRACT FROM AUTHOR]

Rationale: Selective serotonin reuptake inhibitors (SSRIs) are the first choice of treatment for anxiety-like disorders. However, which aspects of anxiety are affected by SSRIs is not yet fully understood. Objective: We aimed to systematically review the effect of six clinically effective SSRIs on four aspects of unconditioned anxiety: approach-avoidance behaviour (elevated plus maze), repetitive behaviour (marble burying), distress behaviour (ultrasonic vocalization), and activation of the autonomous nervous system (stress-induced hyperthermia). Methods: We identified publications by searching Medline and Embase databases and assessed the risk of bias. A random effects meta-analysis was performed and moderator effects were analysed with Bayesian penalized meta-regression. Results: Our search yielded 105 elevated plus maze, 63 marble burying, 11 ultrasonic vocalization, and 7 stress-induced hyperthermia articles. Meta-analysis suggested that SSRIs reduce anxiety-like behaviour in the elevated plus maze, marble burying and ultrasonic vocalization test and that effects are moderated by pre-existing stress conditions (elevated plus maze) and dose dependency (marble burying) but not by duration of treatment or type of SSRI. The reporting quality was low, publication bias was likely, and heterogeneity was high. Conclusion: SSRIs seem to reduce a broad range of unconditioned anxiety-associated behaviours. These results should be interpreted with caution due to a high risk of bias, likely occurrence of publication bias, substantial heterogeneity and limited moderator data availability. Our review demonstrates the importance of including bias assessments when interpreting meta-analysis results. We further recommend improving the reporting quality, the conduct of animal research, and the publication of all results regardless of significance. [ABSTRACT FROM AUTHOR]

[Display omitted] • Warming impacted both individual and group behavior in juvenile C. carpio. • Long-term warming had a more pronounced impact on the decline of swimming activity. • Transcriptomics revealed that warming affected cytoskeletal organization, mitochondrial regulation, and energy metabolism in brain. • Synaptic transmission and signal transduction pathways were the key signature to explain behavior changes under warming. Global warming is increasing interest in how aquatic animals can adjust their physiological performance and cope with temperature changes. Therefore, understanding the behavioral changes and molecular underpinnings in fish under warming is crucial for both the individual and groups survival. This could provide experimental evidence and resource for evaluating the impact of global warming. Three genetic families of common carp (Cyprinus carpio) were generated. These juveniles were constructed short-term (4 days) and long-term (30 days) warming groups to investigate the effects of warming on behavioral responses and to elucidate the potential underlying mechanisms of warming-driven behavior. Behavioral tests were used to explore the effects of short- and long-term exposure to warming on the swimming behavior of C. carpio. Brain transcriptome combined with measurement of nervous system activity was used to further investigated the comprehensive neuromolecular mechanisms under warming. Long-term warming groups had a more significant impact on the decline of swimming behavior in juvenile C. carpio. Furthermore, brain comparative transcriptomic analysis combined with measurement of nervous system activity revealed that genes involved in cytoskeletal organization, mitochondrial regulation, and energy metabolism are major regulators of behavior in the juvenile under warming. Importantly, especially in the long-term warming groups, enrichment analysis of associated gene expression suggested functional alterations of synaptic transmission and signal transduction leading to swimming function impairment in the central nervous system, as revealed by behavioral tests. Our study provides evidence of the neurogenomic mechanism underlying the decreased swimming activity in juvenile C. carpio under warming. These findings have important implications for understanding the impacts of climate change on aquatic ecosystems and the organisms that inhabit them. [ABSTRACT FROM AUTHOR]

Aim: The aim of the nationwide study was to describe paediatric drug utilisation in Sweden. Methods: Drug prescriptions dispensed to all children aged 0–17 years in 2019 were analysed using data from the Swedish National Prescribed Drug Register. Results: We retrieved data on 2 180 508 unique children. Nearly 4.6 million prescriptions were dispensed to children aged 0–17 years, and 52% of these were to boys. Just under half of the children (47%) were dispensed at least one drug: 48% of girls and 45% of boys (p < 0.01). More than a third (34%) were dispensed three or more different drugs during 2019. The number of dispensed prescriptions per 1000 children was higher in boys than girls up to 12 years of age (p < 0.01), and the opposite trend was observed from 13 years and above, even when we excluded contraceptives (p < 0.01). The most common therapeutic areas were drugs for the respiratory tract (25%), namely antihistamines, antiasthmatics and cough medication. These were followed by psychoanaleptics and melatonin for the nervous system (19%) and dermatologicals (16%), namely cortisone creams and emollients. Conclusion: Paediatric drug use was common, and a considerable proportion of children were dispensed multiple drugs. [ABSTRACT FROM AUTHOR]

Tri(1,3-dichloro-2-propyl)phosphate (TDCPP) is one of the most widely used organophosphorus flame retardants in consumer products. TDCPP has been confirmed to be neurotoxic, but its mechanism has not been clarified and may be related to mitophagy. AMBRA1 can promote neurological autophagy, but whether AMBRA1 is involved in the mechanism of TDCPP-induced neurotoxicity has not been elucidated. In this study, the optimal neuronal damage model was established by exposing mice hippocampal neurons to TDCPP. Furthermore, on the basis of this model, siRNA was used to knock down AMBRA1. Combined with qRT-PCR and Western blot techniques, we identified AMBRA1-mediated mitophagy-induced neuronal damage in vitro mechanism. The experimental results indicated that TDCPP treatment for 24 h led to a decrease in the cell viability of mouse hippocampal neurons, causing neuronal damage. Meanwhile, TDCPP exposure increased autophagy marker proteins p62 and LC3B, and down-regulated mitochondrial DNA ND1 damage and TOMM20 protein, suggesting that TDCPP exposure promoted mitophagy. In addition, TDCPP exposure led to changes in the expression of AMBRA1 and the key factors of mitophagy, FUNDC1, PINK1, and PARKIN, whereas mitophagy was inhibited after knockdown of AMBRA1. The research results indicated that exposure to TDCPP induced neuronal damage and promoted mitophagy. The mechanism may be that AMBRA1 promoted mitophagy in neuronal cells through the PARKIN-dependent/non-dependent pathway. This study revealed the toxic effects of TDCPP on the nervous system and its potential molecular mechanisms, which provided important clues for further understanding the mechanism of action of AMBAR1-mediated mitophagy. [ABSTRACT FROM AUTHOR]

Human corticospinal excitability (CSE) modulates during movement, when muscles are active, but also at rest, when muscles are not active. These changes in resting motor system excitability can be transient or longer lasting. Evidence from transcranial magnetic stimulation (TMS) studies suggests even relatively short periods of motor learning on the order of minutes can have lasting effects on resting CSE. Whether individuals are able to return CSE to out-of-task resting levels during the intertrial intervals (ITI) of behavioral tasks that do not include an intended motor learning component is an important question. Here, in twenty-five healthy young adults, we used single-pulse TMS and electromyography (EMG) to measure motor evoked potentials (MEPs) during two different resting contexts: (1) prior to engaging in the response task during which participants were instructed only to rest (out-of-task), and (2) ITI of a choice-reaction time task (in-task). In both contexts, five TMS intensities were used to evaluate possible differences in recruitment of corticospinal (CS) output across a range of inputs. We hypothesized resting state CSE would be greater during ITI than out-of-task rest, reflected in larger MEP amplitudes. Contrary to our hypothesis, we observed no significant difference in MEP amplitudes between out-of-task rest and in-task ITI, and instead found evidence of equivalence, indicating that humans are able to return to a stable motor resting state within seconds after a response. These data support the interpretation that rest is a uniform motor state in the healthy nervous system. In the future, our data may be a useful reference for motor disorder populations with an impaired ability to return to rest. [ABSTRACT FROM AUTHOR]

Weak sensory noise acts on the nervous system and promotes sensory and motor functions. This phenomenon is called stochastic resonance and is expected to be applied for improving biological functions. This study investigated the effect of electrical stimulation on grip force adjustment ability. The coefficient of variation and absolute motor error in grip force was measured during a visuomotor tracking task under different intensities of somatosensory noise. Depending on the style of force exertion, the grip movement used in the visuomotor tracking task consisted of force generation (FG), force relaxation (FR), and constant contraction (Constant) phases. The subthreshold condition resulted in significantly lower coefficient of variation in the Constant phase and motor errors in the FG and Constant phases than the no-noise condition. However, the differences among the other conditions were insignificant. Additionally, we examined the correlation between the motor error in the condition without electrical stimulation and the change in motor error induced by subthreshold electrical stimulation. Significant negative correlations were observed in all FG, FR, and Constant phases. These results indicated that somatosensory noise had a strong effect on subjects with large motor errors and enhanced the grip force adjustment ability. By contrast, subjects with small motor errors had weak improvement in motor control. Although the effect of subthreshold noise varies depending on the individual differences, stochastic resonance is effective in improving motor control ability. [ABSTRACT FROM AUTHOR]

Bisphenol-A (BPA) is a synthetically manufactured phenolic substance that is very widely employed in producing polycarbonate polymers and epoxy resins which further can be found in numerous items of daily use such as foodstuff and their containers, beverages, milk, audit rolls, dental fillings and so forth. Additionally, it is present in the air we breathe-in. The studies have reported that BPA produces toxic impacts on reproductive, cardiovascular, endocrine, renal, gastrointestinal, immune, respiratory, nervous and skeletal system. In the current literature review, we have targeted to highlight the protective role of herbs in opposition to BPA toxicity. The gift of nature-'Plants' seem to be very efficient and potential agents to overcome the BPA induced toxicity as they themselves are devoid of adverse effects. Plants contain a mixture of phyto-molecules which together act to provide a synergistic effect. Further, we have explained the signaling mechanisms implicated in BPA toxicity. Even though, multiple mechanisms involved in BPA toxicity have been examined, no particular target therapy for this toxicity is available at present. Thus, naturally occurring substances may be looked at in the future for restorative use to mitigate the deleterious and negative consequences of exposure to BPA. [ABSTRACT FROM AUTHOR]

Fluctuations in estradiol levels at each stage of life in women are considered one of the causes of mental diseases through their effects on the central nervous system. During menopause, a decrease in estradiol levels has been reported to affect the serotonin nervous system and induce depression‐like and anxiety symptoms. However, the regulation of brain and behaviour during childhood and adolescence is poorly understood. Moreover, the role of oestrogen receptors α and β in the regulation of the serotonergic nervous system has been reported, but little is known about the involvement of G protein‐coupled receptor 30. Therefore, in this study, we used an ovariectomized childhood mouse model to analyse behaviour and investigate the effects on the serotonin nervous system. We showed that ovariectomy surgery at 4 weeks of age, which is the weaning period, induced a decrease in spontaneous locomotor activity during the active period and a preference for novel mice over familiar mice in the three‐chamber social test at 10 weeks of age. In addition, the administration of G‐1, a protein‐coupled receptor 30 agonist, to ovariectomized mice suppressed spontaneous locomotor activity and the preference for novel mice. Furthermore, we demonstrated that childhood ovariectomy induces increased tryptophan hydroxylase gene expression in the raphe nucleus and increased serotonin release in the amygdaloid nucleus, and administration of G‐1 ameliorated these effects. Our study suggests that G protein‐coupled receptor 30‐mediated regulation of serotonin synthesis is involved in changes in activity and social‐cognitive behaviour due to decreased estradiol levels during childhood. [ABSTRACT FROM AUTHOR]

Arthritogenic alphaviruses pose a significant public health concern due to their ability to cause joint inflammation, with emerging evidence of potential neurological consequences. In this review, we examine the immunopathology and immune evasion strategies employed by these viruses, highlighting their complex mechanisms of pathogenesis and neurological implications. We delve into how these viruses manipulate host immune responses, modulate inflammatory pathways, and potentially establish persistent infections. Further, we explore their ability to breach the blood-brain barrier, triggering neurological complications, and how co-infections exacerbate neurological outcomes. This review synthesizes current research to provide a comprehensive overview of the immunopathological mechanisms driving arthritogenic alphavirus infections and their impact on neurological health. By highlighting knowledge gaps, it underscores the need for research to unravel the complexities of virus-host interactions. This deeper understanding is crucial for developing targeted therapies to address both joint and neurological manifestations of these infections. [ABSTRACT FROM AUTHOR]

Panax ginseng (P. ginseng), a traditional and highly valued botanical drug, has been used for thousands of years and is known around the world for its uses in food, medicine, and healthcare. The comprehensive study of P. ginseng is crucial for the quality assurance of medicinal materials and optimal resource utilization. Despite being present in trace amounts, P. ginseng volatile oil has a wide range of chemical metabolites with important medicinal potential. The volatile oil has shown promise in defending the cardiovascular system, as well as in terms of its ability of antibacterial, anti-aging, anti-platelet coagulation, anti-inflammatory, support the nervous system nutritionally, and shield it from harm. Due to its low composition and lack of thorough investigation, P. ginseng volatile oil's therapeutic applicability is still restricted although it exhibited many benefits. This review aims to provide insights into the chemical composition, extraction processes, pharmacological effects, and mechanisms of action of P. ginseng volatile oil, and to provide theoretical support and guidelines for future research and clinical application. [ABSTRACT FROM AUTHOR]

Neurology and connective tissue are intimately interdependent systems and are critical in regulating many of the body’s systems. Unlocking their multifaceted relationship can transform clinical understanding of the mechanisms involved in multisystemic regulation and dysregulation. The fascial system is highly innervated and rich with blood vessels, lymphatics, and hormonal and neurotransmitter receptors. Given its ubiquity, fascia may serve as a “watchman,” receiving and processing information on whole body health. This paper reviews what constitutes fascia, why it is clinically important, and its contiguous and interdependent relationship with the nervous system. Unquestionably, fascial integrity is paramount to human locomotion, interaction with our environment, bodily sense, and general physical and emotional wellbeing, so an understanding of the fascial dysregulation that defines a range of pathological states, including hypermobility syndromes, autonomic dysregulation, mast cell activation, and acquired connective tissue disorders is critical in ensuring recognition, research, and appropriate management of these conditions, to the satisfaction of the patient as well as the treating practitioner. [ABSTRACT FROM AUTHOR]

Background and objectives: Observational studies have suggested that a multitude of pathological processes and biomolecules are involved in the initiation and development of epilepsy, and ULK3 is linked to the nervous system. However, it remains uncertain whether this association between ULK3 and epilepsy is causal and the direction of any causal relationship. This study employs a two-sample Mendelian randomization (MR) method to investigate the relationship between ULK3 and the risk of epilepsy. Methods: We analyzed genome-wide association study (GWAS) summary statistics for ULK3 (sample size = 3,301), focal epilepsy (sample size = 39,348), and generalized epilepsy (sample size = 33,446). Bidirectional MR analyses were conducted to explore these relationships. We selected a set of single nucleotide polymorphisms (SNPs) with an association threshold of less than 1 × 10−5 as instrumental variables for further analysis. Various MR methods, including Inverse Variance Weighted, Weighted Median, MR-Egger Regression, Simple Model, Weighted Model, and Robust Adjustment Profile Score were used. Sensitivity analyses were performed to ensure the robustness of the results. Results: Our MR analyses revealed a causal relationship where an increased level of ULK3 was associated with a decreased risk of focal epilepsy (odds ratio = 0.92, 95% confidence interval: 0.86–1.00, p = 0.041). No significant heterogeneity (Q = 7.85, p = 0.165) or horizontal pleiotropy (Egger regression intercept = 0.0191, p = 0.415) was detected. However, in the reverse analysis, we found no significant causal effect of focal epilepsy on ULK3 (p > 0.05). Furthermore, no significant causation was identified between ULK3 and generalized epilepsy (p > 0.05). Conclusion: This study suggests a causal relationship between ULK3 and the risk of focal epilepsy from a genetic perspective. Nevertheless, further investigation is needed to understand the role of ULK3 in epilepsy fully. [ABSTRACT FROM AUTHOR]

Coordinated movement requires the nervous system to continuously compensate for changes in mechanical load across different conditions. For voluntary movements like reaching, the motor cortex is a critical hub that generates commands to move the limbs and counteract loads. How does cortex contribute to load compensation when rhythmic movements are sequenced by a spinal pattern generator? Here, we address this question by manipulating the mass of the forelimb in unrestrained mice during locomotion. While load produces changes in motor output that are robust to inactivation of motor cortex, it also induces a profound shift in cortical dynamics. This shift is minimally affected by cerebellar perturbation and significantly larger than the load response in the spinal motoneuron population. This latent representation may enable motor cortex to generate appropriate commands when a voluntary movement must be integrated with an ongoing, spinally-generated rhythm. Motor cortex generates commands for voluntary movement, but its role in tasks driven by a spinal pattern generator remains unclear. Here, the authors identify a cortical signal for inertial load in locomoting mice that is decoupled from motor output. [ABSTRACT FROM AUTHOR]

The synaptic response of ZnO/HfZrO memristor devices to electrical stimuli was studied. It was found that the frequency of the stimuli affects the rate of current increase, which can be explained by the cluster state of oxygen vacancies at the interface of ZnO/HfZrO. This variation in the synaptic response due to stimulus frequency was consistent with the dynamic adjustment of tolerance thresholds observed in the human brain's response to environmental stimuli. The rate of change in current, representing the sensitivity to stimuli, mirrors the biological nervous system's reaction to environmental changes, such as Ebbinghaus forgetting behavior. Additionally, frequent irregular changes in stimuli lead to a reduced lifespan of the devices, highly resembling the biological lifetime-injure on frequent environmental fluctuations. These findings highlight the memristors' significant similarity to biological nerves in response to stimuli, confirming their tremendous potential in bionic synaptic simulation applications. [ABSTRACT FROM AUTHOR]

Muscle wasting is a universal hallmark of aging which is displayed by a wide range of organisms, although the causes and mechanisms of this phenomenon are not fully understood. We used Drosophila to characterize the phenomenon of spontaneous muscle fiber degeneration (SMFD) during aging. We found that SMFD occurs across diverse types of somatic muscles, progresses with chronological age, and positively correlates with functional muscle decline. Data from vital dyes and morphological markers imply that degenerative fibers most likely die by necrosis. Mechanistically, SMFD is driven by the damage resulting from muscle contractions, and the nervous system may play a significant role in this process. Our quantitative model of SMFD assessment can be useful in identifying and validating novel genetic factors that influence aging-related muscle wasting. [ABSTRACT FROM AUTHOR]

Intra- or extracellular aggregates of proteins are central pathogenic features in most neurodegenerative disorders. The accumulation of such proteins in diseased brains is believed to be the end-stage of a stepwise aggregation of misfolded monomers to insoluble cross-ß fibrils via a series of differently sized soluble oligomers/protofibrils. Several studies have shown how a-synuclein, amyloid-ß, tau and other amyloidogenic proteins can act as nucleating particles and thereby share properties with misfolded forms, or strains, of the prion protein. Although the roles of different protein assemblies in the respective aggregation cascades remain unclear, oligomers/protofibrils are considered key pathogenic species. Numerous observations have demonstrated their neurotoxic effects and a growing number of studies have indicated that they also possess seeding properties, enabling their propagation within cellular networks in the nervous system. The seeding behavior of oligomers differs between the proteins and is also affected by various factors, such as size, shape and epitope presentation. Here, we are providing an overview of the current state of knowledge with respect to the "prion-like" behavior of soluble oligomers for several of the amyloidogenic proteins involved in neurodegenerative diseases. In addition to providing new insight into pathogenic mechanisms, research in this field is leading to novel diagnostic and therapeutic opportunities for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsCentral nervous system dysfunction is common in longstanding hereditary transthyretin amyloidosis (ATTRv) caused by the V30M (p.V50M) mutation. Neuropathology studies show leptomeningeal amyloid deposition and cerebral amyloid angiopathy (CAA). Brain MRI is widely used in the assessment of Aβ associated CAA but there are no systematic studies with brain MRI in ATTRv amyloidosis.we performed 3 T brain MRIs in 16 patients with longstanding (>14 years) ATTRV30M. We additionally retrospectively reviewed 48 brain MRIs from patients followed at our clinic. CNS symptoms and signs were systematically accessed, and MRIs were blindly reviewed for ischaemic and haemorrhagic lesions.in the prospective cohort, we found white matter hyperintensities in 8/16 patients (50%, Fazekas score> =1). There were no relevant microbleeds, large ischaemic or haemorrhagic lesions or superficial siderosis. In the retrospective cohort, microbleeds were found in 5/48 patients (10,4%), two of which with > =20 microbleeds. White matter hyperintensities were found in 20/48 cases (41.7%). White matter lesions, microbleeds and cortical atrophy were not associated with disease duration.white matter hyperintensities are common in ATTRV30M, irrespective of disease duration. Haemorrhagic lesions are rare, even in patients with longstanding disease, suggesting the existence of other risk factors. [ABSTRACT FROM AUTHOR]

Background: Patients suffering from neurological symptoms after COVID-19 vaccination (post-COVID-19 vaccination syndrome (PCVS)) have imposed an increasing challenge on medical practice, as diagnostic precision and therapeutic options are lacking. Underlying autoimmune dysfunctions, including autoantibodies, have been discussed in neurological disorders after SARSCoV-2 infection and vaccination. Here, we describe the frequency and targets of autoantibodies against peripheral nervous system tissues in PCVS. Methods: Sera from50 PCVS patients with peripheral neurological symptoms after COVID-19 vaccination and 35 vaccinated healthy controls were used in this study. IgG autoreactivity was measured via indirect immunofluorescence assays on mouse sciatic nerve teased fibers. The frequencies of autoantibodies were compared between groups using Fisher's exact test. Serum anti-ganglioside antibodies were measured in ganglioside blots. Autoantibody target identification was performed using immunoprecipitation coupled to mass spectrometry. Subsequent target confirmation was conducted via cell-based assays and ELISA. Results: Compared with controls, PCVS patients had a significantly greater frequency of autoantibodies against peripheral nervous system structures (9/50 (18%) vs 1/35(3%); p=0.04). Autoantibodies bound to paranodes (n=5), axons (n=4), Schmidt-Lanterman incisures (n=2) and Schwann cell nuclei (n=1). Conversely, antibodies against gangliosides were absent in PCVS patients. Target identification and subsequent confirmation revealed various subunits of neurofilaments as well as DFS-70 as autoantibody epitopes. Conclusion: Our data suggest that autoantibodies against nervous system tissue could be relevant in PCVS patients. Autoantibodies against neurofilaments and cell nuclei with so far non-established links to this disease spectrum should be further elucidated to determine their biomarker potential. [ABSTRACT FROM AUTHOR]

In the neurosciences, concepts play an important role in the conception and direction of research. Among the theoretical notions and direction of research, plasticity stands out because of the multiple ways in which scientists use it to describe and interpret how the nervous system changes and adapts to different requirements. The occurrence of different conceptualizations of plasticity in the scientific literature during the second half of the twentieth century and up to the present was investigated using bibliometric methods. Throughout the period analyzed, synaptic plasticity has remained the dominant conceptualization of plasticity. However, scientists have continued to introduce novel plasticity concepts reflecting the scientific advances they have made in understanding the dynamic nature of the nervous system. The conceptual evolution of plasticity documents that the view of the adult nervous system as immutable has been replaced by an understanding of the nervous system as capable of lifelong change and adaptation. [ABSTRACT FROM AUTHOR]

In the nervous system, alternative RNA processing is particularly prevalent, which results in the expression of thousands of transcript variants found in no other tissue. Neuron-specific RNA-binding proteins co-transcriptionally regulate alternative splicing, alternative polyadenylation, and RNA editing, thereby shaping the RNA identity of nervous system cells. Recent evidence suggests that interactions between RNA-binding proteins and cis-regulatory elements such as promoters and enhancers play a role in the determination of neuron-specific expression profiles. Here, we discuss possible mechanisms through which transcription and RNA processing cross-talk to generate the uniquely complex neuronal transcriptome, with a focus on alternative 3'-end formation. [ABSTRACT FROM AUTHOR]

There is such a vast proliferation of scientific theories of consciousness that it is worrying some scholars. There are even competitions to test different theories, and the results are inconclusive. Consciousness research, far from converging toward a unifying framework, is becoming more discordant than ever, especially with respect to theoretical elements that do not have a clear neurobiological basis. Rather than dueling theories, an integration across theories is needed to facilitate a comprehensive view on consciousness and on how normal nervous system dynamics can develop into pathological states. In dealing with what is considered an extremely complex matter, we try to adopt a perspective from which the subject appears in relative simplicity. Grounded in experimental and theoretical observations, we advance an encompassing biophysical theory, MaxCon, which incorporates aspects of several of the main existing neuroscientific consciousness theories, finding convergence points in an attempt to simplify and to understand how cellular collective activity is organized to fulfill the dynamic requirements of the diverse theories our proposal comprises. Moreover, a computable index indicating consciousness level is presented. Derived from the level of description of the interactions among cell networks, our proposal highlights the association of consciousness with maximization of the number of configurations of neural network connections --constrained by neuroanatomy, biophysics and the environment-- that is common to all consciousness theories. [ABSTRACT FROM AUTHOR]

The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual's genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2, two autosomal recessive MPDZ and CCDC88C). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner's fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions Acetylcholine receptor antibody (AChR‐Ab) detection is crucial in myasthenia gravis (MG) diagnosis and, currently, the radioimmunoassay (RIA) is the gold standard. However, RIA may detect AChR‐Ab against nonpathogenic intracellular epitopes. In this study, we performed fixed cell‐based assay (F‐CBA) in RIA‐AChR‐Ab positive subjects without MG symptoms, to assess whether F‐CBA could show a higher specificity compared to RIA in detecting pathogenic Abs.We reviewed medical records of patients referred to our MG outpatient clinic because of RIA‐AChR‐Ab detection. MG diagnosis was based on clinical examination, electrophysiology and Ab detection. AChR‐Abs were tested by RIA in the whole cohort. Serum samples from RIA‐positive asymptomatic subjects were retested by F‐CBA.Of 605 subjects who tested RIA‐AChR‐Ab positive, MG diagnosis was confirmed in 599. Six subjects were RIA‐AChR‐Ab positive although they had never had MG symptoms; in four of these subjects AChR‐Abs were not detected by F‐CBA, whereas the remaining two (both non‐MG thymoma cases) were positive also by F‐CBA.RIA false positivity for AChR‐Ab is very rare. Previous literature has demonstrated that F‐CBA has higher sensitivity than RIA for MG, especially in ocular cases. Our preliminary results show that, in rare instances, F‐CBA may be more specific than RIA for MG diagnosis. [ABSTRACT FROM AUTHOR]

Neurological diseases are expected to become the leading cause of death in the next decade. Although little is known about it, the interaction between oxidative stress and inflammation is harmful to the nervous system. To find an advanced tool for neural genetics, mouse haploid neural stem cells (haNSCs) from the somite of chimeric mouse embryos at E8.5 is established. The haNSCs present a haploid neural progenitor identity for long‐term culture, promising to robustly differentiate into neural subtypes and being able to form cerebral organoids efficiently. Thereafter, haNSC mutants via a high‐throughput approach and screened targets of oxidative stress is generated using the specific mutant library. Deletion of Nfkbia (the top hit among the insertion mutants) reduces damage from reactive oxygen species (ROS) in NSCs exposed to H2O2. Transcriptome analysis revealed that Atp2b4 is upregulated significantly in Nfkbia‐null NSCs and is probably responsible for the observed resistance. Additionally, overexpression of Atp2b4 itself can increase the survival of NSCs in the presence of H2O2, suggesting that Atp2b4 is closely involved in this resistance. Herein, a powerful haploid system is presented to study functional genetics in neural lineages, shedding light on the screening of critical genes and drugs for neurological diseases. [ABSTRACT FROM AUTHOR]

Migraine, a primary headache disorder whose mechanism remains incompletely understood, appears to involve the activation of the trigeminovascular system (TS) during attacks. Research suggests that inflammatory processes mediated by the immune system may play a role in migraine pathophysiology. Neuroinflammation is often associated with migraine attacks, with cytokines serving as crucial mediators in the process. Elevated levels of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), have been observed in the blood and cerebrospinal fluid of individuals experiencing migraine attacks. These cytokines have the capacity to sensitize pain pathways in the brain, thereby increasing sensitivity to pain stimuli. This phenomenon, known as central sensitization, is believed to contribute to the intensity and persistence of migraine pain. Kynurenines, endogenous mediators of glutamatergic mechanisms, can significantly influence the pathophysiology of primary headache disorders. The kynurenine system is collectively known as the kynurenine pathway (KP), which can act on multiple receptors, such as glutamate receptors, aryl hydrocarbon receptors (AhRs), G protein-coupled receptors 35 (GPR35), and α-7 nicotinic acetylcholine (α7 nACh) receptors. These receptors are also found on various cells of the immune system, so the role of the KP in the pathomechanism of primary headaches may also be mediated through them. In this review, our goal is to show a possible link between the receptors of the KP and immune system in the context of inflammation and migraine. Migraine research in recent years has focused on neuropeptides, such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as potential pathogenic factors and possible therapeutic approaches. These peptides share many similarities in their characteristics and roles. For instance, they exhibit potent vasodilation, occur in both the peripheral and central nervous systems, and play a role in transmitting nociception and neurogenic inflammation. The investigation of potential connections between the aforementioned neuropeptides and the kynurenine pathway could play a significant role in uncovering the pathomechanism of migraine and identifying new drug candidates. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence of insomnia among nurses with long COVID-19, analyze the potential risk factors and establish a nomogram model. Methods: Nurses in Ningbo, China, were recruited for this study. General demographic information and insomnia, burnout, and stress assessment scores were collected through a face-to face questionnaire survey administered at a single center from March to May 2023. We used LASSO regression to identify potential factors contributing to insomnia. Then, a nomogram was plotted based on the model chosen to visualize the results and evaluated by receiver operating characteristic curves and calibration curves. Results: A total of 437 nurses were recruited. 54% of the nurses had insomnia according to the Insomnia Severity Index (ISI) score. Eleven variables, including family structure, years of work experience, relaxation time, respiratory system sequelae, nervous system sequelae, others sequelae, attitudes toward COVID-19, sleep duration before infection, previous sleep problems, stress, and job burnout, were independently associated with insomnia. The R-squared value was 0.464, and the area under the curve was 0.866. The derived nomogram showed that neurological sequelae, stress, job burnout, sleep duration before infection, and previous sleep problems contributed the most to insomnia. The calibration curves showed significant agreement between the nomogram models and actual observations. Conclusion: This study focused on insomnia among nurses with long COVID-19 and identified eleven risk factors related to nurses' insomnia. A nomogram model was established to illustrate and visualize these factors, which will be instrumental in future research for identifying nurses with insomnia amid pandemic normalization and may increase awareness of the health status of healthcare workers with long COVID-19. [ABSTRACT FROM AUTHOR]

Background Purpose Electrical stimulation of the gut has been investigated in recent decades with a view to treating various gastro‐intestinal motility disorders including, among others, gastric electrical stimulation to relieve nausea and vomiting associated with gastroparesis and sacral neuromodulation to treat fecal incontinence and/or constipation. Although their symptomatic efficacy has been ascertained by randomized controlled trials, their mechanisms of action are not fully understood.This review summarizes the past year's literature on the mechanisms of action of gut electrical stimulation therapies, including their impact on the gut‐brain axis. [ABSTRACT FROM AUTHOR]

Introduction: Epilepsy is a widespread disease requiring long-term drug treatment. The aim of this study was to collect information on reported suspected adverse drug reactions (sADRs) of antiseizure medications (ASMs) and study their seriousness and outcomes in various system organ classifications (SOCs). We intended to compare old and new ASMs’ ADRs. Methods: Using EudraVigilance (EV) database, we extracted line listings of reported sADRs with different ASMs over the period from January 2012 to December 2021. The list of ASMs was compiled according to the Anatomical therapeutic chemical classification system. The Medical Dictionary for Regulatory Activities version 24.0 was used for determining the SOCs of individual reported preferred terms (PTs) sADRs. In addition, we calculated the Reporting Odds Ratio (ROR), 95% confidence interval (95% CI), p-value (statistically significant if p< 0.05) and chi-square statistics. Results: A total of 276,694 reports were contained in the exported line listings which included 1,051,142 individual sADRs reported as PTs such as seizure (3.49%), drug ineffective (2.46%), somnolence (1.32%), dizziness (1.29%) and represented four SOCs: nervous system disorders (19.26%), general disorders and administration site conditions (14.39%), psychiatric disorders (11.29%) and injury, poisoning and procedural complications (9.79). Among patients, the age group between 18 and 64 years had the highest percentage (52.40%), followed by those aged over 64 years (18.75%). Of all the reported PTs, 882,706 (83.98%) had reported seriousness. Old ASMs had a significant positive association with “caused/prolonged hospitalisation”, “congenital anomaly”, “disabling”, “life threatening” and “results in death”, while new ASMS with ‘other medically important condition’. There were 386 (0.04%) PTs related to Sudden Unexpected Death in Epilepsy (SUDEP). Conclusion: In our study, we examined 10 years’ reported sADRs of ASMs in the EV international database. The majority of PTs were serious. Old ASMs were generally more commonly associated with undesired outcomes and seriousness. Considering their expected seriousness and outcomes, the safety profile of the different ASMs, can play a cardinal role in the selection of ASMs. [ABSTRACT FROM AUTHOR]

Neurons coordinate inter-tissue protein homeostasis to systemically manage cytotoxic stress. In response to neuronal mitochondrial stress, specific neuronal signals coordinate the systemic mitochondrial unfolded protein response (UPRmt) to promote organismal survival. Yet, whether chemical neurotransmitters are sufficient to control the UPRmt in physiological conditions is not well understood. Here, we show that gamma-aminobutyric acid (GABA) inhibits, and acetylcholine (ACh) promotes the UPRmt in the Caenorhabditis elegans intestine. GABA controls the UPRmt by regulating extra-synaptic ACh release through metabotropic GABAB receptors GBB-1/2. We find that elevated ACh levels in animals that are GABA-deficient or lack ACh-degradative enzymes induce the UPRmt through ACR-11, an intestinal nicotinic α7 receptor. This neuro-intestinal circuit is critical for non-autonomously regulating organismal survival of oxidative stress. These findings establish chemical neurotransmission as a crucial regulatory layer for nervous system control of systemic protein homeostasis and stress responses. Here, Cornell et al. reveal specific neurotransmitters (gamma-aminobutyric acid and acetylcholine) that regulate the ability of animals to manage metabolic stress through an intestinal acetylcholine receptor. [ABSTRACT FROM AUTHOR]

Simple Summary: Rare earth elements (REEs) are widely used in various fields of human activity. However, data from many studies indicate the harmful effects of REEs on humans and animals, including the nervous system. In this study, we estimated the REE content in hair samples of children living on the Kola Peninsula (Murmansk region) in the vicinity of the Lovozersky REE Mining and Processing Plant, and we linked the REE content in children's bodies to the prevalence of the nervous system diseases in Lovozersky District. We observed a higher prevalence of nervous system diseases (episodic paroxysmal disorders (G40–G47), cerebral palsy (G80–G83), epilepsy and status epilepticus (G40–G41)) in children aged 15–17 years in Lovozersky District compared to other territories of the Murmansk region. Indirect evidence of the link between REE content in hair samples of children and nervous system diseases is provided by data in the literature. According to these data, REEs are deposited in the brain structures responsible for the function of the nervous system, thus impairing them. This investigation highlights the relevance of studying the role of REEs in nervous system diseases, and it points to the need for the further research in this area. The aim of this study is to assess the rare earth element (REE) content in hair samples of children living in Lovozero village, near an REE mining site, and the possible effects of REEs on the prevalence of nervous system diseases in Lovozersky District (Murmansk region, Kola Peninsula). Fifty-three school-age children were recruited for the analysis of REE content in hair samples. REE (Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) content was estimated by means of inductively coupled plasma mass spectrometry (ICP-MS). The analysis of REE content in the hair of children living in Russia, Kazakhstan, and China indicated REE intake from the environment. The possible contribution of REEs to nervous system disorders is supported by the link between the REE content in hair samples of children living near REE mining areas (China) and the manifestation of cognitive disorders in these children. It is also found that the prevalence of nervous system diseases in children aged 15–17 years is higher in Lovozersky District compared to the other districts of the Murmansk region. In this paper, the possible contribution of REEs to the prevalence of episodic paroxysmal disorders (G40–G47), cerebral palsy (G80–G83), and epilepsy and status epilepticus (G40–G41) is discussed. [ABSTRACT FROM AUTHOR]

Background and main body: Although interactions between the nervous and immune systems have been recognized decades ago, it has become increasingly appreciated that neuroimmune crosstalk is among the driving factors of multiple pulmonary inflammatory diseases including acute lung injury (ALI). Here, we review the current understanding of nerve innervations towards the lung and summarize how the neural regulation of immunity and inflammation participates in the onset and progression of several lung diseases, especially ALI. We then present advancements in the development of potential drugs for ALI targeting neuroimmune interactions, including cholinergic anti‐inflammatory pathway, sympathetic‐immune pathway, purinergic signalling, neuropeptides and renin‐angiotensin system at different stages from preclinical investigation to clinical trials, including the traditional Chinese medicine. Conclusion: This review highlights the importance of considering the therapeutic strategy of inflammatory diseases within a conceptual framework that integrates classical inflammatory cascade and neuroimmune circuits, so as to deepen the understanding of immune modulation and develop more sophisticated approaches to treat lung diseases represented by ALI. Key points: The lungs present abundant nerve innervations.Neuroimmune interactions exert a modulatory effect in the onset and progression of lung inflammatory diseases, especially acute lung injury.The advancements of potential drugs for ALI targeting neuroimmune crosstalk at different stages from preclinical investigation to clinical trials are elaborated.Point out the direction for the development of neuroimmune pharmacology in the future. [ABSTRACT FROM AUTHOR]

Neutral sphingomyelinase‐2 (nSMase2), gene name sphingomyelin phosphodiesterase‐3 (Smpd3), is a key regulatory enzyme responsible for generating the sphingolipid ceramide. The function of nSMase2 in the brain is still controversial. To better understand the functional roles of nSMase2 in the aging mouse brain, we applied RNA‐seq analysis, which identified a total of 1462 differentially abundant mRNAs between +/fro and fro/fro, of which 891 were increased and 571 were decreased in nSMase2‐deficient mouse brains. The most strongly enriched GO and KEGG annotation terms among transcripts increased in fro/fro mice included synaptogenesis, synapse development, synaptic signaling, axon development, and axonogenesis. Among decreased transcripts, enriched annotations included ribosome assembly and mitochondrial protein complex functions. KEGG analysis of decreased transcripts also revealed overrepresentation of annotations for Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington disease (HD). Ingenuity Pathway Analysis (IPA) tools predicted lower susceptibility to these neurodegenerative disorders, as well as predictions agreeing with stronger synaptic function, learning, and memory in fro/fro mice. The IPA tools identified signaling proteins, epigenetic regulators, and microRNAs as likely upstream regulators of the broader set of genes encoding the affected transcripts. It also revealed 16 gene networks, each linked to biological processes identified as overrepresented annotations among the affected transcripts by multiple analysis methods. Therefore, the analysis of these RNA‐seq data indicates that nSMase2 impacts synaptic function and neural development, and may contribute to the onset and development of neurodegenerative diseases in middle‐aged mice. [ABSTRACT FROM AUTHOR]

This study examined the effectiveness of the ketogenic diet as a therapeutic intervention for cerebral hemorrhage recovery. This randomized controlled trial consisted of 108 patients, recruited for the study, 54 patients were assigned to the intervention group, which followed a ketogenic diet and 54 patients were assigned to the control group, which followed a regular diet. The intervention group followed a ketogenic diet while the control group followed a regular diet. We evaluated the effects of the ketogenic diet on neurological function, metabolic profile, cognitive function, depression levels, physical activity levels, and the occurrence of adverse events over a 6-month period. The results demonstrated significant improvements in the intervention group compared to the control group, with notable reductions in National Institutes of Health Stroke Scale scores and enhancements in Modified Rankin Scale scores at both 3 and 6 months, indicating improved neurological function and faster functional recovery. Ketogenic diet intervention also resulted in significant enhancements in cognitive performance and depression scores, indicating further advantages for mental health, and increased the level of physical activity compared to the control group. Overall, our results demonstrate that the ketogenic diet shows potential as an additional treatment for cerebral hemorrhage recovery. It provides notable advantages in terms of neurological and functional recovery, metabolic health, cognitive performance, and emotional well-being. [ABSTRACT FROM AUTHOR]

The Finnish web-based Meds75+ database supports rational, safe and appropriate prescribing to older adults in primary care. This article describes the content and updating process of Meds75+ and demonstrates its applicability in everyday clinical practice. Meds75+ contains a classification (A–D) and recommendation texts for 450–500 drug substances when used in the treatment of older adults aged 75 years or older. The content of Meds75+ is continually updated. Each assessment of a drug substance begins with a structured collection of available information and research evidence. After that, an interdisciplinary expert panel discusses the classification and recommendation using a consensus method. A rolling 3-year updating cycle guarantees that all drug substances are reviewed regularly. Most drug substances are classified as class A (41%) (suitable, e.g. bisoprolol) or as class C (37%) (suitable with specific precautions, e.g. ibuprofen). One-fifth (20%) of the substances are in class D (avoid use, e.g. diazepam). Most commonly, older adults have purchased substances affecting the alimentary tract and metabolism (17%), the nervous system (16%) and the cardiovascular system (15%). In Finland, the proportion of older adults using class D substances (37%) has not changed between the years 2019 and 2022. Meds75+ has potential to support safer and more effective use of medications for older adults, since it offers up-to-date information on drug substances for healthcare professionals. [ABSTRACT FROM AUTHOR]

Individuals with chronic ankle instability (CAI) demonstrate altered movement patterns when their vision is disturbed during simple tasks, such as single-legged standing and walking. However, it remains unclear whether visual disruption by stroboscopic glasses alters movement patterns during landing-cutting movements, considered highly demanding sport maneuvers that mimic a typical athletic movement. To identify altered lower extremity kinematics and muscle activation when vision is disrupted by stroboscopic glasses during landing-cutting tasks in individuals with CAI. Case-control study. Laboratory. A total of 18 individuals with CAI (age = 22.3 ± 2.3 years, height = 1.75 ± 0.1 m, mass = 72.5 ± 9.8 kg) and 18 matched healthy controls (age = 21.7 ± 2.3 years, height = 1.75 ± 0.1 m, mass = 71.9 ± 10.3 kg). All participants performed 5 trials of a landing-cutting task with (SV) and without (NSV) stroboscopic glasses. Frontal- and sagittal-plane lower extremity kinematics and 6 lower extremity muscle activations during the stance phase of a landing-cutting task in the SV and NSV conditions. Individuals with CAI demonstrated more ankle-inversion angle from 18% to 22% and from 60% to 100% of the stance phase and more peroneus longus activation from initial contact to 18% of the stance phase under the SV condition than under the NSV condition. We observed no differences in knee- and hip-joint angles between the visual conditions for both groups. When wearing stroboscopic glasses, individuals with CAI showed altered movement patterns, including increased ankle-inversion angle and peroneus longus activation during the stance phase of a landing-cutting task. The results suggest that they may lack the ability to reweight sensory information to adapt their movement to visual disruption. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the impact of human umbilical cord-derived MSCs (hUC-MSCs) on motor function in children with cerebral palsy (CP). The study enrolled 152 children with CP who received up to two courses of five hUC-MSCs injections. Children's motor functions were assessed with the Gross Motor Function Measure (GMFM), 6-Minute Walk Test (6-MWT), Timed Up and Go test (Up&Go test), and Lovett's test, and mental abilities were assessed with the Clinical Global Impression (CGI) scale. Data collected at visit 1 (baseline) and visit 5 (after four injections) were analyzed retrospectively. After four hUC-MSCs administrations, all evaluated parameters improved. The change in GMFM score, by a median of 1.9 points (IQR: 0.0–8.0), correlated with age. This change was observed in all GFMCS groups and was noticed in all assessed GMFM areas. A median increase of 75 m (IQR: 20.0–115.0) was noted on the 6-MWT, and this correlated with GMFM score change. Time on the Up&Go test was reduced by a median of 2 s (IQR: −3 to − 1) and the change correlated with age, GMFM score at baseline, and the difference observed on the 6-MWT. Results of Lovett's test indicated slight changes in muscle strength. According to the CGI, 75.5% (96/151) of children were seriously (level VI) or significantly ill (level V) at the 1st visit, with any improvement observed in 63.6% (96/151) of patients at the 5th visit, 23.8% (36/151) with improvement (level II) or great improvement (level I). In conclusion, the application of hUC-MSCs generally enhanced functional performance, but individual responses varied. The therapy also benefited children with high level of disability but not to the same extent as the initially less disabled children. Although younger patients responded better to the treatment, older children can also benefit. Trial Registration 152/2018/KB/VII and 119/2021/KB/VIII. Retrospective registration in ClinicalTrials: ongoing. [ABSTRACT FROM AUTHOR]

Simple Summary: In our study, we aimed to understand the role of non-coding RNA in egg production by analyzing the transcriptome of chickens. We collected tissues from both low-yielding and high-yielding Bian chickens, focusing on the hypothalamus, pituitary, and ovaries, which are key to reproduction. Using advanced sequencing technology, we identified circular RNAs that differed between high and low egg producers. Our results revealed that these circRNAs are involved in crucial processes like cell development, nervous system function, and protein regulation. We also discovered networks of RNA interactions that may influence egg production. These findings enhance our understanding of the genetic factors that control egg production, potentially leading to improved breeding strategies for better poultry production and health, benefiting farmers and consumers alike. The hypothalamic–pituitary–ovarian (HPO) axis plays a pivotal role in the regulation of egg production in chickens. In addition to the traditional understanding of the HPO axis, emerging research highlights the significant role of circRNAs in modulating the functions of this axis. In the study, we collected hypothalamus, pituitary, and ovarian tissues from low-yielding and high-yielding Bian chickens for transcriptome sequencing. We identified 339, 339, and 287 differentially expressed (DE) circRNAs with p_value < 0.05 and |log2 (fold change)| ≥ 1 in hypothalamus, pituitary, and ovarian tissues. The Gene Ontology (GO) enrichment analysis for the source genes of DE circRNAs has yielded multiple biological process (BP) entries related to cell development, the nervous system, and proteins, including cellular component morphogenesis, cell morphogenesis, nervous system development, neurogenesis, protein modification process, and protein metabolic process. In the top 30 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we observed the enrichment of the GnRH signaling pathway in both the hypothalamus and the pituitary, solely identified the GnRH secretion pathway in the pituitary, and discovered the pathway of oocyte meiosis in the ovary. Furthermore, given that circRNA primarily functions through the ceRNA mechanism, we constructed ceRNA regulatory networks with DE circRNAs originating from the GnRH signaling pathway, GnRH secretion, ovarian steroidogenesis, steroid hormone biosynthesis, and the estrogen signaling pathway. Finally, several important ceRNA regulatory networks related to reproduction were discovered, such as novel_circ_003662-gga-let-7b/miR-148a-3p/miR-146a-5p/miR-146b-5p and novel_circ_003538-gga-miR-7464-3p-SLC19A1. This study will contribute to advancements in understanding the involvement of circRNAs in the HPO axis, potentially leading to innovations in improving egg production and poultry health. [ABSTRACT FROM AUTHOR]

Acute coronavirus disease 2019 (COVID-19) is paralleled by a rise in the peripheral levels of neurofilament light chain (NfL), suggesting early nervous system damage. In a cohort of 103 COVID-19 patients, we studied the relationship between the NfL and peripheral inflammatory markers. We found that the NfL levels are significantly predicted by a panel of circulating cytokines/chemokines, including CRP, IL-4, IL-8, IL-9, Eotaxin, and MIP-1ß, which are highly up-regulated during COVID-19 and are associated with clinical outcomes. Our findings show that peripheral cytokines influence the plasma levels of the NfL, suggesting a potential role of the NfL as a marker of neuronal damage associated with COVID-19 inflammation. [ABSTRACT FROM AUTHOR]

CX3CL1 is one of the 50 up-to-date identified and characterized chemokines. While other chemokines are produced as small, secreted proteins, CX3CL1 (fractalkine) is synthetized as a transmembrane protein which also leads to a soluble form produced as a result of proteolytic cleavage. The membrane-bound protein and the soluble forms exhibit different biological functions. While the role of the fractalkine/CX3CR1 signaling axis was described in the nervous system and was also related to the migration of leukocytes to sites of inflammation, its actions are controversial in cancer progression and anti-tumor immunity. In the present review, we first describe the known biology of fractalkine concerning its action through its cognate receptor, but also its role in the activation of different integrins. The second part of this review is dedicated to its role in cancer where we discuss its role in anti-cancer or procarcinogenic activities. [ABSTRACT FROM AUTHOR]

Neurexins and their canonical binding partners, neuroligins, are localized to neuronal pre-, and post-synapses, respectively, but less is known about their role in driving behaviors. Here, we use the nematode C. elegans to show that neurexin, but not neuroligin, is required for avoiding specific chemorepellents. We find that adults with knockouts of the entire neurexin locus exhibit a strong avoidance deficit in response to glycerol and a weaker defect in response to copper. Notably, the C. elegans neurexin (nrx-1) locus, like its mammalian homologs, encodes multiple isoforms, α and γ. Using isoform-specific mutations, we find that the γ isoform is selectively required for glycerol avoidance. Next, we used transgenic rescue experiments to show that this isoform functions at least partially in the nervous system. We also confirm that the transgenes are expressed in the neurons and observe protein accumulation in neurites. Furthermore, we tested whether these mutants affect the behavioral responses of juveniles. We find that juveniles (4th larval stages) of mutants knocking out the entire locus or the α-isoforms, but not γ-isoform, are defective in avoiding glycerol. These results suggest that the different neurexin isoforms affect chemosensory avoidance behavior in juveniles and adults, providing a general principle of how isoforms of this conserved gene affect behavior across species. [ABSTRACT FROM AUTHOR]

Reindeer have long been served as vital subsistence resources for inhabitants of Arctic and subarctic regions owing to their domestication. However, the evolutionary relationships and divergence times among different reindeer populations, genetic traits that distinguish domesticated reindeer, and factors that contribute to their relative docility compared with that of other Cervidae specie, remain unclear. In this study, we sequenced the genomes of 32 individuals from wild and domestic reindeer populations that inhabit Arctic and subarctic regions. We found that reindeer experienced 2 or more independent domestication events characterized by weak artificial selection pressure and limited significant differences in genomic parameters between wild and domestic populations. Alterations in conserved noncoding elements in the reindeer genomes, particularly those associated with nervous system development, may have contributed to their domestication by rendering the nervous system less responsive. Together, our results suggest that inherent species-specific traits, rather than intense artificial selection, may have played a significant role in the relatively docile behavior of reindeer and offer valuable insights into the domestication process of these animals. [ABSTRACT FROM AUTHOR]

Charles Bell was famous for the discovery of the separate motor and sensory roots of the spinal and facial nerves, although in recent years his right to priority has been challenged by historians and scientists. But Charles Bell did discover something even if has not been accorded the status of a scientific fact. Between 1821 and 1823 he unveiled the 'respiratory nervous system', a distinct system of nerves that acted as the 'organ of the passions', which he then elaborated upon in his 1824 Essays on the Anatomy and Philosophy of Expression. As Bell and his allies attempted to claim priority in the spinal and facial nerves, the respiratory nerves were pushed to the background, subordinated to the motor and sensory nerves. This essay, therefore, redefines Charles Bell's major discovery as the 'respiratory nerves', providing a detailed description of their anatomy and physiology and the way in which they underwrote Bell's theory of the emotions. It also demonstrates how his aesthetics were intertwined with his research programme. It then connects the respiratory nerves to Thomas Dixon's assertion that Bell was one of the founders of the modern psychological category of the emotions, providing a deeper and more nuanced genealogy of the emotions, including the impact that Bell had upon William James's seminal article 'What is an Emotion?' [ABSTRACT FROM AUTHOR]

GPCRs operate across highly specialized subcellular compartments in neurons, with the need for precise control of their spatiotemporal properties. G protein-binding proteins can reshape GPCR signaling dynamics through general and receptor-specific mechanisms. GPCRs undergo crosstalk with each other through direct and indirect mechanisms, which are themselves subject to regulation by G protein-binding proteins and receptor-specific scaffolds. Synapse-specific mechanisms, including local trafficking, trans-synaptic interactions, scaffold networks, and targeting to cilia, further expand the repertoire of neuromodulatory GPCR regulation. A rapidly evolving toolset is enabling studies of neuromodulatory GPCRs with unprecedented precision. In the nervous system, G protein-coupled receptors (GPCRs) control neuronal excitability, synaptic transmission, synaptic plasticity, and, ultimately, behavior through spatiotemporally precise initiation of a variety of signaling pathways. However, despite their critical importance, there is incomplete understanding of how these receptors are regulated to tune their signaling to specific neurophysiological contexts. A deeper mechanistic picture of neuromodulatory GPCR function is needed to fully decipher their biological roles and effectively harness them for the treatment of neurological and psychiatric disorders. In this review, we highlight recent progress in identifying novel modes of regulation of neuromodulatory GPCRs, including G protein- and receptor-targeting mechanisms, receptor–receptor crosstalk, and unique features that emerge in the context of chemical synapses. These emerging principles of neuromodulatory GPCR tuning raise critical questions to be tackled at the molecular, cellular, synaptic, and neural circuit levels in the future. [ABSTRACT FROM AUTHOR]