NeuroSci

Peripheral nerve injury initiates a complex cascade of events coordinating immune responses, extracellular matrix (ECM) remodeling, and neuronal repair. While β2-microglobulin (B2M) is well known for its role in MHC class I-mediated antigen presentation and CD8⁺ T-cell differentiation, its potential contributions to non-immune processes remain underexplored. In this study, we investigated the role of B2M in peripheral nerve regeneration using a chronic constriction injury (CCI) model in wild-type and B2M-deficient (B2M-KO) mice. Flow cytometry, RNA sequencing (RNA-seq), and quantitative PCR (qPCR) were performed to assess T-cell subset dynamics and gene expression following injury. Flow cytometric analysis showed that CD3⁺CD4⁺ and CD3⁺CD8⁺ T-cell populations increased by day 7 post-injury. While CD3⁺CD4⁺ T-cell expansion occurred in both groups, a significant increase in CD3⁺CD8⁺ T cells was observed only in wild-type mice. RNA-seq analysis at 3 days post-injury—prior to substantial T-cell accumulation—revealed marked downregulation of ECM-related genes in B2M-KO mice, including collagens, matrix-associated proteins, and other key ECM components. KEGG analysis identified suppression of ECM–receptor interaction, PI3K-Akt, and TGF-β signaling pathways. qPCR confirmed reduced expression of Thbs1 in B2M-KO mice. These findings suggest that B2M plays a critical, CD8⁺ T-cell-independent role in regulating ECM dynamics and regenerative signaling during early nerve repair, expanding the conceptual framework of B2M’s function beyond classical immune roles. Full article

Background: We aimed to determine the utility of different electrodiagnostic (EDx) methods in diagnosing meralgia paresthetica (MP). Methods: Twenty-nine MP patients and 26 controls were included. Sensory nerve action potential (SNAP) and somatosensory evoked potential (SEP) of the lateral femoral cutaneous nerve (LFCN) and tibial SEPs were measured bilaterally. Results: At least one LFCN SNAP was unobtainable in 18 patients (62%) and two controls (8%). In all remaining 11 patients, SNAPs were abnormal at least unilaterally. By contrast, LFCN SEPs were recorded bilaterally in all subjects and were abnormal in 16 patients (sensitivity 48%). Patients’ tibial SEP latency was significantly larger than that of controls (p < 0.001). Conclusions: LFCN NCSs are superior to SEP in the evaluation of MP. However, SEP studies may be useful in old (>60 years) and obese subjects with unobtainable LFCN SNAP. Longer tibial SEP points to subclinical neuropathy in MP patients predisposed to LFCN entrapment. Full article

At the 14th Panhellenic Conference on Alzheimer’s Disease and 6th Mediterranean Conference on neurodegenerative diseases, we experienced an exciting journey, following the patient through the stages of their neurodegenerative disease: onset, diagnosis, progression, and eventual outcome. Fighting alongside him are researchers, doctors, psychologists, biologists, chemists, pharmacists, nurses, trainers, physiotherapists, speech therapists, occupational therapists, electrical engineers, architects, and other scientists, even actors and musicians, who aim to prevent and cure the disease, limit its progression, and improve the quality of life of those affected by it. Among them, their caregivers stand out as the most dedicated companions. In a collection of abstracts that reflects the work of all of the above, we capture the results of our biennial scientific meeting, which, thanks to them, is constantly evolving in a promising way. Full article

Transcranial pulse stimulation (TPS) is a non-invasive neuromodulation method that uses, high-intensity acoustic shockwaves to deliver focused mechanical stimulation to neural tissue with minimal thermal effects. The mechanism of action includes but is not limited to promotion of blood flow and angiogenesis through mechanotransduction. Clinical data to date are limited and preliminary. In Alzheimer’s disease (AD), TPS has demonstrated cognitive and mood improvements in pilot studies and secondary endpoint analysis in first randomized trials. The enhancement of gamma-band oscillations and network connectivity has been reported. Clinical observations in Parkinson’s disease (PD) suggest TPS as a hypothesis-generating approach to address non-motor symptoms—such as depression, cognitive decline, and the freezing of gait—through theoretical modulation of basal ganglia–cortical circuits. TPS is CE-marked in Europe for AD and shows a favorable safety profile; however, ethical considerations arise from the limited evidence base, potential impairment of patient autonomy and judgment in dementia, and the risk of withholding established treatments. TPS should only be offered under structured scientific protocols or within patient registries to ensure rigorous oversight. Ensuring that consent processes account for cognitive capacity, and that TPS is applied as adjunct rather than replacement therapy, is paramount. Future research must include large-scale randomized controlled trials (RCTs), standardize stimulation protocols, deepen mechanistic insight, and embed robust ethical frameworks. Full article

Emotional attunement, or emotional co-regulation in a relationship, can manifest as interpersonal neural synchrony, where partners exhibit similar anti-phase or phase-shifted brain activity. In adult romantic relationships, emotional attunement may differ according to relationship satisfaction. No study has examined how relationship satisfaction difference influences interpersonal neural synchrony. This exploratory pilot study on 17 couples (unmarried Chinese undergraduate couples in a Southeast Asian university) investigated whether relationship satisfaction difference influenced interpersonal neural synchrony during a shared emotive experience. Each couple wore an fNIRS cap to measure brain activity in their prefrontal cortex (PFC) while co-viewing seven videos intended to evoke positive, negative or neutral emotions. We found preliminary evidence that relationship satisfaction difference modulated interpersonal neural synchrony in the right ventral PFC regions, including the right ventromedial PFC (involved in the encoding of emotional values to stimuli and emotional regulation), right ventrolateral PFC (involved in voluntary emotional regulation) and the right orbitofrontal cortex (involved in processing of emotional experiences and regulation of emotions). This suggested that couples with mismatched relationship satisfaction displayed greater interpersonal neural synchrony, possibly due to mutual social cognitive processes when viewing emotive videos together. Further studies can replicate the findings with larger, diverse samples. Full article

Background: Disparities in neuro-oncological care between high-income and low- and middle-income countries (LMICs) are well documented, yet region-specific data from Latin America remain limited. This review evaluates epidemiologic trends, access to care, and systemic challenges in brain tumor management across Latin American LMICs, using Argentina as a case study. Methods: A systematic review of peer-reviewed literature was conducted focusing on brain tumor incidence, mortality, risk factors, and availability of diagnostics and treatments in Latin America. Socioeconomic, cultural, and systemic barriers were also analyzed. Results: Latin America exhibits some of the highest global brain tumor mortality rates, with Brazil reporting age-standardized rates exceeding 4.5 per 100,000. Glioblastomas are frequently diagnosed at younger ages, often in the fifth decade of life, compared to the global average. Meningioma incidence has increased by 15–20% over the last decade, yet region-wide data remain fragmented. Access to neuroimaging, neurosurgery, radiotherapy, and chemotherapy is limited, with up to 60% of patients relying solely on under-resourced public health systems. Less than 30% of hospitals in rural areas have MRI availability, and continuous professional training is infrequent. Innovative adaptations, such as awake craniotomy, are used in some LMIC centers in response to equipment scarcity. Conclusions: Brain tumor care in Latin America is hindered by limited epidemiological data, restricted access to diagnostics and treatment, and insufficient workforce training. Targeted investments in healthcare infrastructure, international educational collaborations, and policy-level reforms are critical to reducing disparities and improving outcomes in neuro-oncology across the region. Full article

Bisphenol A diglycidyl ether (BADGE) is the main component of epoxy resin and is used for the inner coating of canned foods and plastic food containers. BADGE can easily migrate from containers and result in food contamination; the compound is known as an endocrine-disrupting chemical. We previously reported that maternal exposure to bisphenol A bis (2,3-dihydroxypropyl) ether (BADGE·2H₂O), which is the most detected BADGE derivative not only in canned foods but also in human specimens, during gestation and lactation, could accelerate neuronal differentiation in the cortex of fetuses and induce anxiety-like behavior in juvenile mice. In this study, we investigated the effects of low-dose BADGE·2H₂O (1–100 pM) treatment on neurites and the mechanism of neurite outgrowth in cortical neurons. BADGE·2H₂O exposure significantly increased the number of dendrites and neurite length in cortical neurons; these accelerating effects were inhibited by estrogen receptor (ER) antagonist ICI 182,780 and G-protein-coupled estrogen receptor (GPER) antagonist G15. BADGE·2H₂O down-regulated Hes1 expression, which is a transcriptional repressor, and increased levels of neuritogenic factor neurogenin-3 (Ngn3) in the cortical neurons; the changes were significantly blocked by G15. These data suggest that direct BADGE·2H₂O exposure can accelerate neuritogenesis and outgrowth in cortical neurons through down-regulation of Hes1 and by increasing Ngn3 levels through ERs, particularly GPER. Full article

Gliomas are the most common central nervous system tumors and account for 30% of all primary brain tumors, 80% of all malignant ones, and the vast majority of deaths that are caused by brain tumors. Among them, glioblastoma multiforme has the most aggressive and invasive course. Due to its heterogeneity, it is difficult to treat, and one of the reasons for this are glioma stem cells (GSCs). Therapies such as radiotherapy and chemotherapy are used to treat gliomas but do not bring the expected results. Therefore, treatments targeting glioma stem cells are emerging. A promising strategy is to target GSCs with natural compounds. This review aims to describe the problem of glioma stem cells, the treatment of gliomas, and therapies based on natural compounds, which are promising for the future. Full article

In the face of the limitations in pharmacological and surgical interventions for neurological conditions such as Parkinson’s and Alzheimer’s disease, patients are increasingly turning to non-pharmacological and alternative therapies to manage their symptoms and improve their quality of life. This shift underscores the urgent need for accessible, effective, and affordable treatments. This literature review examines a range of alternative and personalized therapies, including game therapy, animal-assisted therapy, dance therapy, art therapy, music therapy, aroma therapy, and shinrin-yoku therapy. These modalities have demonstrated promising results in mitigating symptoms and enhancing well-being among individuals grappling with neurological disorders. Moreover, these therapies offer a holistic approach that complements traditional medical interventions, underscoring the importance of integrating diverse treatment modalities. Despite their historical roots in non-clinical settings, their potential in modern clinical practice remains untapped. The findings suggest the necessity for further research, particularly large cohort studies, to validate the efficacy of these personalized therapies and advocate for their widespread adoption. In an era marked by escalating healthcare costs, the exploration of alternative therapies presents a compelling avenue for enhancing patient care while simultaneously addressing economic challenges within the healthcare system. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, heterogeneous at the molecular level and characterized by diverse and complex pathological features. Such features are known to accumulate silently in the brain over years or even decades before the onset of detectable symptoms. Despite long years of intense research activities, the disease remains orphaned of either disease-modifying therapies or a specific blood test capable of predicting the disease in the pre-symptomatic stages. This disappointing outcome of such efforts can be attributed to a number of factors. One of these factors is the failure of earlier research to capture the heterogeneity of the disease. Such failure has the direct consequence of poor patient stratification, which in turn impacts negatively on the development of specific and effective therapy. The second factor is the absence of detailed and accurate information on proteins and associated post-translational modifications, which may influence the initiation and progress of the disease. Recent studies have demonstrated that the quantification of various isoforms of phosphorylated tau protein in plasma and other biofluids can be considered as potential biomarkers for the early detection of Alzheimer’s disease. Mass spectrometry-based proteomics and immunoassay-based multiplex proteomics are the two technologies in current use for probing the human proteome, both in tissues and biofluids. In the present review, we discuss the contribution of MS-based proteomics to efforts aimed at the identification and eventual characterization of the heterogeneity of the disease, and the key role of the same technique in the analysis of protein post-translational modifications associated with the disease is also discussed. Full article

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms of fibroblastic origin. In this study, we report a rare case of cervical SFT in a pediatric patient, a rare phenomenon since the incidence is particularly rare in pediatric patients according to the literature. Typical radiological features of the lesion may lead to misdiagnosis. Image study and immunohistochemistry are crucial for its correct diagnosis. Their imaging characteristics often resemble meningiomas or schwannomas, making differential diagnosis challenging. Immunohistochemical markers such as CD34 and STAT6 remain essential for definitive diagnosis. Full article

Insomnia is common in individuals with opioid use disorder (OUD). Biopsychosocial factors are important in sleep health, yet this intersection has yet to be fully elucidated in people on buprenorphine for OUD. The objective is to report on patient-reported biopsychosocial factors among people with and without insomnia, specifically among women and men in outpatient OUD treatment. The parent study enrolled adults stabilized on buprenorphine from February 2022–September 2023. Scores of ≥11 on the Insomnia Severity Index (ISI) indicated clinically significant insomnia. Differences were detected by the presence of insomnia, stratified by men and women, using chi-squared and Fisher’s exact tests. Of the overall participants (N = 130), most (n = 77; 59.2%) met the criteria for clinically significant insomnia. Women with insomnia were more likely to report social stressors including discrimination for substance use (p = 0.040), food insecurity (p = 0.032), and transportation difficulties accessing healthcare (p = 0.043) than women without insomnia. Men with insomnia were more likely to report financial difficulties accessing healthcare (p = 0.023) than men without insomnia. These findings provide a unique perspective to consider in the development and implementation of sleep interventions for women and men receiving medication treatment for OUD. Full article

SH-SY5Y neuroblastoma cells can be effectively differentiated into a neuronal phenotype using retinoic acid (RA) and brain-derived neurotrophic factor (BDNF), making them a valuable in vitro model for studying neuronal differentiation. This study aimed to investigate the electrophysiological properties of SH-SY5Y cells following prolonged differentiation, with a focus on membrane characteristics, evoked action potentials, and the functionality of cellular components such as N-methyl-D-aspartate (NMDA) receptor. Whole-cell patch-clamp recordings were employed to evaluate ionic currents and action potentials in embryonic mouse cortical neurons (mCNs) and in both differentiated and undifferentiated SH-SY5Y neuroblastoma cells. Differentiated SH-SY5Y cells exhibited neurite outgrowth, evoked action potential firing, and functional NMDA receptor-mediated currents. Notably, atorvastatin significantly modulated the duration and firing of action potentials as well as NMDA receptor-mediated currents in differentiated SH-SY5Y cells. These findings highlight that neuronally differentiated SH-SY5Y cells expressing functional NMDA receptor-mediated currents serve as a robust and convenient model for investigating the molecular mechanisms of NMDA receptor function and for screening pharmacological agents targeting these receptors. Full article

Background: Parkinson’s disease (PD) is a debilitating neurodegenerative disorder affecting millions of people worldwide. PD results in motor and cognitive dysfunction. While there is no proven cure for PD, it is widely agreed that aerobic exercises and occupations can help slow the progression of the disease and keep some motor-related symptoms from developing. The most effective forms of exercise to slow the progression of motor symptoms in Parkinson’s disease have also been studied. Research Question: This research article aims to compare the differences in outcomes of exercise on cognitive outcomes in Parkinson’s Disease, as evaluated by meta-analysis. Methods: Key terms were Parkinson’s Disease and exercise terms. These search terms were then entered to electronic databases—Ovid MEDLINE, SCOPUS, and CINAHL—from March 2018 to May 2023. An ancestral bibliography was also performed. Results: Two reviewers screened the title and abstract records (n = 528) found in the initial search. Our review identified 18 studies which met inclusion criteria for meta-analysis. The meta-analysis found an effect of exercise on cognition of patients with PD (d = −0.03) which was not significant (CI95% of −0.13 < µ < 0.08; p > 0.05, as the CI includes zero). Additionally, the homogeneity analysis was not significant (Q (17) = 2.83; p > 0.05). Full article

Background: The Dementia Attitude Scale (DAS) is a validated instrument used to capture the affective, behavioural, and cognitive components of attitudes toward people living with dementia (PLwD). This study conducts confirmatory and exploratory factor analyses (CFA and EFA) of the DAS assessed by caregivers of PLwD and BPSD enrolled in the RECage multicentre clinical trial. Methods: The baseline questionnaire was completed by 485 caregivers (29.7% male, 70.3% female), from six European countries, reflecting diverse cultural contexts. CFA tested the two-factor structure of the original model, while EFA thoroughly explored the factor structure. Results: The CFA results showed a poor model fit, with significant deviations from ideal values for RMSEA (0.0861), SRMSR (0.0781), and CFI (0.7117), showcasing an inadequate representation of the data. EFA revealed a three-factor structure, explaining the 45.2% variance for social comfort, 28.8% for social discomfort, and 25.9% for dementia knowledge. The social comfort items reflected positive caregiver attitudes toward PLwD, while social discomfort captured feelings of discomfort and uncertainty about caregiving. Dementia knowledge included items related to understanding dementia’s symptoms and needs. Conclusions: The three-factor model highlights the importance of emotional comfort, knowledge of dementia, and social discomfort as key dimensions in caregiver attitudes. Full article

Since its discovery, TRPC6 has been associated with a variety of physiological and pathophysiological processes in different tissues. It functions as a non-selective cation channel and belongs to the group of TRP channels. Its importance in the development of pain hypersensitivity is becoming increasingly apparent. This condition has already been associated with increased expression of TRPC6 in dorsal root ganglia. Apart from the fact that most of the evidence has been obtained from samples of animal origin, it remains unclear whether the channel is also expressed in peripheral nerves outside the dorsal root ganglia. The aim of this work was therefore to examine peripheral nerves from human samples for TRPC6. For this purpose, samples of both the sciatic and ulnar nerves were taken from a total of eight body donors and analyzed by immunohistochemistry. Both longitudinal and transverse sections were obtained from the samples and stained. In total, 43 of 48 histological sections showed a positive immunosignal. There were no major differences between the sciatic and ulnar nerves with regard to staining. There was a slight difference in the staining intensity of transverse and longitudinal sections. The longitudinal sections of both nerves were consistently colored slightly more intensely. However, the inter-individual differences between the donors were more pronounced. Interestingly, the samples of a donor who suffered from chronic pain syndrome during his lifetime were particularly strongly stained. This is consistent with the knowledge gained to date, largely from animal experiments, that the channel shows increased expression in pain conditions in dorsal root ganglia. In the future, TRPC6 could therefore be a target in pain therapy. Full article

Limbic encephalitis (LE) associated with anti-LGI1 antibodies is an autoimmune disorder characterized by memory decline, behavioral changes, and temporal lobe epilepsy. Faciobrachial dystonic seizures (FBDS) are a hallmark symptom, often preceding cognitive and psychiatric issues. This report presents an 80-year-old male with LGI1 encephalitis, initially manifesting as FBDS. A lung adenocarcinoma was diagnosed two months after the onset of neurological symptoms. Clinical and paraclinical data, including MRI and [18]FDG PET imaging, are described. The patient responded to immunotherapy, including steroids and plasma exchange, along with tumor resection. Following treatment, neurological symptoms resolved, except for mild anxiety and apathy. Further research is needed to determine whether LGI1 encephalitis may occasionally have a paraneoplastic origin, potentially influencing screening and management strategies. Full article

This paper proposes a theoretical model of meaning-making grounded in proprioceptive awareness and embodied imagination, arguing that human cognition is inherently multimodal, anticipatory, and sensorimotor. Drawing on Peircean semiotics, Lotman’s model of cultural cognition, and current research in neuroscience, we show that readiness to act—a proprioceptively grounded anticipation of movement—plays a fundamental role in the emergence of meaning, from perception to symbolic abstraction. Contrary to traditional approaches that reduce language to a purely symbolic or visual system, we argue that meaning arises through the integration of sensory, motor, and affective processes, structured by axial proprioceptive coordinates (vertical, horizontal, sagittal). Using Peirce’s triadic model of interpretants, we identify proprioception as the modulatory interface between sensory stimuli, emotional response, and logical reasoning. A study on skilled pianists supports this view, showing that mental rehearsal without physical execution improves performance via motor anticipation. We define this process as proprioceptive resonance, a dynamic synchronization of embodied states that enables communication, language acquisition, and social intelligence. This framework allows for a critique of linguistic abstraction and contributes to ongoing debates in semiotics, enactive cognition, and the origin of syntax, challenging the assumption that symbolic thought precedes embodied experience. Full article

Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex neurodevelopmental disorder with a multifactorial etiology involving genetic, epigenetic, and environmental factors. This review focuses on the current understanding of these contributing elements, examining how they interact to influence ADHD development. Genetic predispositions, environmental exposures, and epigenetic modifications collectively shape the risk and manifestation of the disorder. Despite advancements in research, significant challenges remain in identifying precise mechanisms and translating them into effective treatments. The variability of symptoms across individuals, influenced by factors such as age, gender, and cultural background, further complicates diagnosis and treatment. Addressing these challenges requires a deeper investigation into the underlying causes of ADHD and the development of tailored interventions. This review aims to highlight both the progress made in understanding ADHD etiology and the current gaps in treatment approaches, calling for more targeted research and personalized therapeutic strategies. Full article