Chronic stress disrupts physiological and psychological homeostasis, yet effective therapeutic strategies remain limited. This study investigated the adaptogenic effects of Rhodiola rosea root powder (standardized to 3% salidroside) on stress-induced behavioral and physiological changes in a murine model of chronic mild stress. Female C57BL/6 mice were exposed to a 19-day chronic mild stress protocol and received daily oral supplementation of Rhodiola rosea root powder, administered in gummies to ensure accurate and stress-free intake, or a placebo. At the end of the experiment, behavioral outcomes were assessed using the Elevated Plus Maze (EPM) and Open Field (OF) tests. Compared with stressed controls, stressed treated mice demonstrated significant improvements. In the EPM, treated mice showed significantly higher locomotor activity (greater distance and speed), with more open-arm entries and time, as well as increased head dips, indicating reduced anxiety and enhanced exploration. In the OF test, they also displayed greater locomotion and more center-zone entries, both reaching statistical significance and supporting reduced anxiety-like behavior. These behavioral improvements were accompanied by a significant reduction in serum corticosterone levels, indicating modulation of the physiological stress response. Together, the findings support the anxiolytic and adaptogenic properties of Rhodiola rosea root powder and highlight its potential as a natural intervention for managing chronic stress. Future studies should investigate the long-term efficacy and mechanisms of its bioactive compounds in stress resilience and mental health.

During somatosensory neurogenesis, neurons are born in an unspecialized transcriptional state. Several transcription factors in these cells follow a broad-to-restricted expression trajectory as development proceeds, giving rise to neuron subtypes with different identities. The relevance of this temporal refinement of transcription factor expression remains unclear as the functions of transcription factors with broad-to-restricted expression patterns have been mostly studied in those neuron subtypes in which they remain active. Here we show that Dach1 encodes a bona fide transcription factor with a broad-to-restricted expression pattern retained and required in tactile somatosensory neurons. In developing nociceptors, Prdm12 contributes to Dach1 silencing. Using genetic approaches to prevent its temporal restriction during mouse somatosensory development, we reveal that Dach1 expression refinement is a prerequisite for the acquisition of an appropriate transcriptional profile in those somatosensory neuron subtypes in which it becomes ultimately silenced. These findings highlight the essential role played by Dach1 during somatosensory neuron development and demonstrate that the temporal pattern of broad-to-restricted expression followed by several transcription factors is physiologically important for the development of somatosensory neurons.

INTRODUCTION:Despite the recommendations to use a bio-psycho-social framework, many physiotherapists still manage their patients mainly from a biomedical point of view. The purpose of this study is to analyze the impact of two different e-learning interventions on knowledge, attitudes, and clinical decision-making of physiotherapists managing low back pain (LBP) to increase guideline-consistent care. METHODS:Physiotherapists were allocated (1/1) either to an experimental or a traditional e-learning intervention. Baseline and post-intervention assessment included the Health Care Providers' Pain and Impairment Relationship Scale (HC-PAIRS), Back Pain Attitudes Questionnaire (Back-PAQ), Neurophysiology of Pain Questionnaire (NPQ), and a clinical vignette. Participants had 2 weeks to complete the post-intervention assessment. Statistics were processed using ANCOVA and Fisher's t-tests. RESULTS:Four hundred nineteen physiotherapists were included in the analysis. Mean scores of HC-PAIRS, Back-PAQ, and NPQ significantly improved post-intervention in both groups. There was a significant effect of the intervention type (experimental versus traditional) on the scores of HC-PAIRS (p < .001; η2p = .243) and Back-PAQ (p < .001; η2p = .135) but not on NPQ scores. Return to work, recommendations assessed with the clinical vignette were significantly more guideline-consistent in the experimental group (p < .001) post-intervention. CONCLUSION:An interactive e-learning intervention which includes concrete clinical examples and focused on patient's reassurance, self-management, and importance of screening psycho-social factors had more impact than a traditional e-learning intervention to enhance physiotherapists' knowledge, attitudes, and clinical decision-making regarding LBP.

System xc- (with xCT as specific subunit) is an astrocytic cystine/glutamate antiporter that constitutes the major source of extracellular glutamate in the mouse striatum. We previously reported that young-adult mice lacking xCT (xCT-/- mice) display decreased intracellular glutamate levels in pre- and post-synaptic compartments at corticostriatal synapses as well as impaired corticostriatal neurotransmission, compared to wildtype (xCT+/+) littermates. These changes were accompanied by increased repetitive behavior and reduced social interaction, typical behaviors related to autism spectrum disorder (ASD). Although ASD is reported to be associated with atypical brain aging, we recently showed that xCT-/- mice are protected against age-related hippocampal decline. Therefore, we here investigated whether the corticostriatal impairments and associated ASD-like behavior would be maintained in aged (16-months-old) mice. Genetic deletion of xCT does not affect corticostriatal neurotransmission in aged mice or the morphology of medium-spiny neurons. Except for a slight decrease in synaptic cleft width, the ultrastructure of corticostriatal synapses and intracellular glutamate levels are unaltered in the absence of xCT in aged mice. Accordingly, repetitive and social explorative behavior were comparable between aged xCT+/+ and xCT-/- mice, while the latter showed a reduction in interactions that could be classified as being aggressive or dominant. To conclude, contrary to our previous observations in young-adult mice, corticostriatal neurotransmission and social behavior are no longer impaired in aged xCT-/- mice, most likely because intracellular glutamate levels are no longer different. Moreover, the reduced levels of advanced glycation end-products that we observed in striatal tissue of xCT-/- mice, can protect the xCT-/- brain from age-related pathogenic alterations.

OBJECTIVES:To review the current literature findings dedicated to the toxicity of nano- and microplastics (NMPs) in the upper respiratory tract. DATA SOURCES:PubMED, Cochrane Library and Embase databases. REVIEW METHODS:Three independent investigators conducted the literature search for the documentation and toxicity of NMP in the upper respiratory tract according to the PRISMA statements. Primary outcomes included NMP types, shape, density, sizes, the environment (air, mask wearing, plasticdevice), and the histological and physiological modifications associated with the deposit of NMP. RESULTS:The scoping review included 12 studies (10 clinical, 2 experimental) with 356 human subjects. NMPs were detected in all samples, predominantly as fragments (10-500 μm), except in mask-wearers where fibers predominated. Polypropylene, polycarbonate, and polyurethane were the most common. Clinical studies showed higher NMP density in patients with nasal disorders with an increased permeability of mucosa (rhinosinusitis and allergic rhinitis) than in healthy controls. Mask wearing and nasal lavage devices contributed to NMP deposition. Experimental studies demonstrated NMP cellular internalization with potential physiological disruption, including oxidative stress, autophagy dysfunction, and respiratory microbiome alterations. There was substantial heterogeneity across studies for NMP detection methods. CONCLUSIONS:The current clinical and experimental studies demonstrate that both exposed and unexposed humans have nasal NMP detected in their nasal tissues and fluids. Mask wearing and the use of old plastic nasal lavage devices can contribute to this deposition. While experimental studies suggest changes in tissue and cell physiology, the toxicity of NMP in nasal tissue remains poorly investigated and has not been conclusively demonstrated.

Sensory perception emerges from the integration of multiple inputs from different sensory modalities, a process previously attributed to higher-order cortices. However, increasing evidence suggests that the primary visual cortex also processes nonvisual stimuli. Here, we investigated the response of the primary visual cortex to visual, auditory and somatosensory stimuli in awake, head-fixed mice using evoked local field potentials, multi- and single-unit recordings. Our results demonstrate that the primary visual cortex responds to auditory and somatosensory inputs with distinct frequency band modulations and firing rate patterns across monocular and binocular regions. Notably, somatosensory stimuli elicited the fastest response latencies, suggesting a privileged role in murine sensory processing. Auditory and somatosensory stimuli modulated the primary visual cortex activity similarly to contralateral visual inputs, whereas ipsilateral visual stimulation resulted in weaker responses. These findings indicate that the primary visual cortex is not solely dedicated to vision but also responds to auditory and somatosensory stimuli, supporting a potential role in multisensory processing.

Introduction Neurogenic lower urinary tract (NLUTD), bowel (NBD), and sexual dysfunction (SD) are commonly observed in patients with (pw) multiple sclerosis (MS) and diminish the patients' quality of life (QoL). This systematic review aim to evaluate and discuss the current algorithms for the management of these issues. Methods A systematic review was conducted on the PubMed in June 2024. The primary search criterion was the presence of the term 'algorithm/s' or ‘management/ing’ in the title and/or abstract, followed by the MeSH term 'multiple sclerosis' and a combination of free-text keywords referring to NLUTD, NBD or SD. Results Fifteen articles regarding NLUTD were considered eligible, only one regarding SD while none addressed NBD. Discussion Numerous studies emphasize the profound impact of urinary and bowel symptoms on the QoL and morbidity in pwMS. Few algorithms addressing NLUTD are designed for first-line physicians and addresses the key priorities in MS care. Specific approaches to NBD management in pwMS are lacking. Screening for SD requires a structured assessment to deliver appropriate solutions. Conclusion NLUTD, NBD, and SD are underdiagnosed and undertreated. The implementation of straightforward algorithms for first-line physicians could enhance the management of these common issues, improve the QoL, reduce costs, and ensure appropriate referral to specialists.

In recent years, brain research has indisputably entered a new epoch, driven by substantial methodological advances and digitally enabled data integration and modelling at multiple scales—from molecules to the whole brain. Major advances are emerging at the intersection of neuroscience with technology and computing. This new science of the brain combines high-quality research, data integration across multiple scales, a new culture of multidisciplinary large-scale collaboration, and translation into applications. As pioneered in Europe’s Human Brain Project (HBP), a systematic approach will be essential for meeting the coming decade’s pressing medical and technological challenges. The aims of this paper are to: develop a concept for the coming decade of digital brain research, discuss this new concept with the research community at large, identify points of convergence, and derive therefrom scientific common goals; provide a scientific framework for the current and future development of EBRAINS, a research infrastructure resulting from the HBP’s work; inform and engage stakeholders, funding organisations and research institutions regarding future digital brain research; identify and address the transformational potential of comprehensive brain models for artificial intelligence, including machine learning and deep learning; outline a collaborative approach that integrates reflection, dialogues, and societal engagement on ethical and societal opportunities and challenges as part of future neuroscience research.

INTRODUCTION : The practice of electroneurography is not common in Congolese environment, which makes early diagnosis of peripheral neuropathies such as those due to diabetes difficult. OBJECTIVE To characterize the electroneurography parameters of diabetic subjects in relation to neuropathic pain in comparison with non-diabetic subjects, in the city of Lubumbashi. METHODS A cross-sectional study was conducted in 51 subjects, 25 of whom were diabetic and 26 non-diabetic. Symptoms of neuropathic pain were assessed using the diabetic neuropathy scale and electroneurography tracings were recorded with the Neuro-MEP Micro version 3 device. RESULTS Neuropathic pain was significantly more frequent in diabetic subjects compared to non-diabetic subjects. Electroneurography parameters (amplitude, distal latency and nerve conduction) were significantly altered in diabetics compared to non-diabetics, exhibiting patterns of demyelinating axonal sensory and motor polyneuropathy in the lower limbs as well as focal and multifocal neuropathies. Electroneurography abnormalities not associated with clinical neuropathic pain suggested the possible existence of subclinical forms of diabetic peripheral neuropathy in diabetic subjects while those noted in non-diabetic subjects suggested neuropathic pain of other origins. CONCLUSION Electroneurography combined with the diabetic neuropathy scale can be used to classify diabetic peripheral neuropathy and detect subclinical neuropathic pain; its implementation is required in the Congolese environment. Further studies are needed to determine local references for electroneurography and electroneurography profiles in situations of multiple neuropathic exposures such as in the city of Lubumbashi.

Abstract Introduction: Cognitive and neurobehavioural disorders in children are poorly documented in Haut-Katanga Province, an environment exposed to trace metals. Objective: To characterize children's behaviour in relation to cognitive performance and exposure to trace metals in urban and rural environments. Methods: A cross-sectional study was carried out on fifty-two children aged 6 to 11 years, including thirty children from urban areas, exposed to trace metals, in the city of Lubumbashi and twenty-two children from rural areas presumed to be less exposed to trace metals, but more exposed to malnutrition. The NEPSY-II tests, the Strengths and Difficulties Questionnaire (SDQ-tutor) and blood and urine trace metals spectrometry assays were used. Results: Total behavioural difficulties predominated in rural area, compared to urban environment, while no difference in the stress or impairment related to difficulties was observed between the groups. Children in urban area performed better cognitively than children of rural environment, particularly on the facial affect recognition and on inhibition. Overall, growth nutritional status determined the level of total behavioural difficulties. Cobalt and lead were detected in the blood of children at levels exceeding the upper reference limits of non-occupationally exposed individuals, especially in urban area for cobalt. The presence of metals in urine and blood was correlated in a complex way with behavioral difficulties and cognitive performance. Conclusion: The extent of the behavioural problems, in relation to cognitive performance, and their association with nutritional problems and exposure to trace metals indicate a multifactorial neurodevelopmental origin requiring further study.

During somatosensory neurogenesis, neurons are born in an unspecialized transcriptional state, with several transcription factors following a broad-to-restricted expression dynamic as development proceeds, supporting neuron subtype identities. The relevance of this temporal refinement remains however unclear, these broad-to-restricted transcription factors being selectively involved in neurons in which they are ultimately maintained. Here we found that Dach1 encodes for a bona fide broad-to-restricted transcription factor retained and required in tactile somatosensory neurons. Within developing nociceptors, we demonstrate that Prdm12 contributes to Dach1 extinction. Using genetic approaches to prevent its temporal restriction during somatosensory development, we reveal that Dach1 refinement is a prerequisite for the appropriate transcriptional maturation of somatosensory subtypes from which it becomes ultimately excluded. These findings highlight the essential role played by Dach1 during somatosensory neuron development. They further demonstrate that the broad-to-restricted temporal pattern followed by several transcription factors is physiologically relevant to achieve appropriate transcriptional maturation of somatosensory neurons. ### Competing Interest Statement The authors have declared no competing interest.

Microglial cells, as the primary defense line in the central nervous system, play a crucial role in responding to various mechanical signals that can trigger their activation. Despite extensive research on the impact of chemical signaling on brain cells, the understanding of mechanical signaling in microglia remains limited. To bridge this gap, we subjected microglial cells to a singular mechanical stretch and compared their responses with those induced by lipopolysaccharide treatment, a well-established chemical activator. Here we show that stretching microglial cells leads to their activation, highlighting their significant mechanosensitivity. Stretched microglial cells exhibited distinct features, including elevated levels of Iba1 protein, a denser actin cytoskeleton, and increased persistence in migration. Unlike LPS-treated microglial cells, the secretory profile of chemokines and cytokines remained largely unchanged in response to stretching, except for TNF-α. Intriguingly, a single stretch injury resulted in more compacted chromatin and DNA damage, suggesting potential long-term genomic instabilities in stretched microglia. Using compartmentalized microfluidic chambers with neuronal networks, we observed that stretched microglial cells exhibited enhanced phagocytic and synaptic stripping activities. These findings collectively suggest that stretching events can unlock the immune potential of microglial cells, contributing to the maintenance of brain tissue homeostasis following mechanical injury.

BACKGROUND AND PURPOSE:Slow-acting biogenic amines, such as dopamine, are known to modulate fast neurotransmitters e.g. glutamate. In the striatum, dopamine (DA) interacts with glutamate, influencing neural excitability and promoting synaptic plasticity. The exact mechanism of such interaction is not fully understood. This study investigates, in detail, how dopamine overactivity in dopamine transporter knockout (DAT-/-) rats, alters the homeostasis of the striatal glutamate synapse from a molecular, behavioural and functional point of view. EXPERIMENTAL APPROACH:The expression, localisation, retention and electrophysiological properties of N-methyl-D-aspartate (NMDA) receptors as well as dendritic spine density and morphology were investigated in the striatum of DAT-/- rats, at baseline and after treatment with the non-competitive NMDA receptor antagonist memantine (30 mg kg-1). KEY RESULTS:Dopamine overactivity dramatically reorganises the striatal glutamate synapse, redistributing NMDA receptors in the synapse as typified by reduced synaptic availability and reduced expression of NMDA scaffolding proteins, as well as by increased GluN2B-containing NMDA receptors in the extra synapse. Such changes are accompanied by reduced spine density, suggesting dopamine-induced structural rearrangements. These results converge into a compromised plasticity, as shown by the impaired ability to promote long-term depression (LTD) in the striatum of DAT-/-rats. Notably, memantine counteracts hyperlocomotion, reverses spine alterations and abolishes the extrasynaptic movements of NMDA receptors in the striatum of DAT-/- rats, thus restoring functional LTD. CONCLUSION AND IMPLICATIONS:A hyperdopaminergic condition seems to alter striatal homeostasis by increasing extrasynaptic NMDA receptors. These findings may be relevant to manipulate disorders characterised by elevated dopaminergic activity.

The multimodal approach where cognition is embodied in language, perceptual, motor, and emotional systems is a widely agreed theoretical framework for conceptual representations. However, the lack of work supporting this view of cognition in healthy and pathological aging stands in stark contrast with the ongoing need to understand the factors that uncover semantic degradation in brain pathologies. The aim of this study is to explore the impact of perceptual strength (PS) - i.e., the extent to which a word can be experienced by multiple sensory modalities - in visual word recognition in Alzheimer's disease (AD). Thirty-six healthy participants, 22 participants in the mild stage of AD (AD1) and 20 in the moderate stage (AD2) took part in a lexical decision task with two conditions: words with high vs low PS words. Results showed an interaction effect only between healthy controls and AD1 individuals, revealing that the latter were faster in processing high PS words in contrast to low PS words, while this was not the case for healthy individuals. Furthermore, it was specifically the ratings of the neuropsychological executive and lexical-semantic assessments that predicted these results. However, no results were observed for AD2 participants, suggesting that lexical-semantic degradation was too severe to reveal a PS effect. This study demonstrates the importance of considering the perceptual dimension when examining the conceptual system and opens up new avenues in the exploration of semantic impairment in AD.

BACKGROUND:Clinical practice guidelines promote bio-psychosocial management of patients suffering from low back pain (LBP). The objective of this study was to examine the current knowledge, attitudes and beliefs of physiotherapists about a guideline-adherent approach to LBP and to assess the ability of physiotherapists to recognise signs of a specific LBP in a clinical vignette.METHODS:Physiotherapists were recruited to participate in an online study. They were asked to indicate whether they were familiar with evidence-based guidelines and then to fill in the Health Care Providers' Pain and Impairment Relationship Scale (HC-PAIRS), Back Pain Attitudes Questionnaire (Back-PAQ), Neurophysiology of Pain Questionnaire (NPQ), as well as questions related to two clinical vignettes.RESULTS:In total, 527 physiotherapists participated in this study. Only 38% reported being familiar with guidelines for the management of LBP. Sixty-three percent of the physiotherapists gave guideline-inconsistent recommendations regarding work. Only half of the physiotherapists recognised the signs of a specific LBP.CONCLUSIONS:The high proportion of physiotherapists unfamiliar with guidelines and demonstrating attitudes and beliefs not in line with evidence-based management of LBP is concerning. It is crucial to develop efficient strategies to enhance knowledge of guidelines among physiotherapists and increase their implementation in clinical practice.

Abstract Introduction The African Copperbelt is a site of intense artisanal and industrial mining and refining of copper and cobalt. Based on a preliminary case-control study of erectile dysfunction among mineworkers in the former Katanga province of the Democratic Republic of Congo (Musa et al. Occupational and Environmental Medicine 2020), Objective We further investigated possible factors associated with erectile dysfunction in copper and cobalt miners in the Katanga province. Methods In a cross-sectional study of 138 miners and 140 controls (bakers), we administered questionnaires face-to-face in French or Swahili to obtain socio-demographic and occupational data, and to assess male sexual function [International Index of Erectile Function (IIEF-15)] and marital relation quality [Revised Dyadic Adjustment Scale (DAS)]. We measured trace metals in blood and urine and testosterone and thyroid hormones in serum. Results Miners and bakers had similar median (IQR) age [35.6 y (30.6–40.0)]. Miners had significantly lower scores than bakers for IIEF-15 [66 (49–73) vs 73 (66–74)] and for the three DAS domains (Consensus; Satisfaction; Cohesion). Miners had significantly lower free testosterone (8.1 ng/dL) and thyroxin (13.45 pmol/L) than bakers (9.3 and 14.75, respectively). Factors associated with IIEF- EF scores ≤ 22 were: mining-related job (aOR 2.09, 95% CI 1.14–3.81; p=0.016), work seniority in mining (aOR 1.07, 95% CI 1.02–1.13; p=0.005) and regular use of aphrodisiacs (aOR 2.80, 95% CI 1.56–5.02; p=0.001). Mediation analysis showed that consensus mediated by 50% the relation between work seniority in mining and erectile function. Conclusions Compared to controls, miners had poorer sexual function and marital relation, and lower free testosterone and thyroxin. This may be due to their high exposure to trace metals (especially Pb). Erectile dysfunction is found to be increased by lower consensus in couples possibly due to longer time spent working away from home. Disclosure No

The network formed by the brainstem, cerebellum, and hippocampus occupies a central position to achieve navigation. Multiple physiological functions are implicated in this complex behavior. Among these, control of the eye-head and body movements is crucial. The gaze-holding system realized by the brainstem oculomotor neural integrator (ONI) situated in the nucleus prepositus hypoglossi and fine-tuned by the contribution of different regions of the cerebellum assumes the stability of the image on the fovea. This function helps in the recognition of environmental targets and defining appropriate navigational pathways further elaborated by the entorhinal cortex and hippocampus. In this context, an enigmatic brainstem area situated in front of the ONI, the nucleus incertus (NIC), is implicated in the dynamics of brainstem-hippocampus theta oscillation and contains a group of neurons projecting to the cerebellum. These neurons are characterized by burst tonic behavior similar to the burst tonic neurons in the ONI that convey eye velocity-position signals to the cerebellar flocculus. Faced with these forgotten cerebellar projections of the NIC, the present perspective discusses the possibility that, in addition to the already described pathways linking the cerebellum and the hippocampus via the medial septum, these NIC signals related to the vestibulo-ocular reflex and gaze holding could participate in the hippocampal control of navigation.