AIMS Neuroscience最新文献

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of the upper and lower motor neurons, which leads to muscle atrophy, spasticity, and ultimately respiratory failure. The etiology of ALS remains unclear, though a combination of genetic and environmental factors is suspected. Advances in understanding ALS pathophysiology, including the role of RNA metabolism, mitochondrial dysfunction, and glutamate toxicity, have paved the way for new research directions. While Riluzole offers limited survival benefits, there is no cure, and treatment remains mostly supportive. This article summarizes the current understanding of ALS in terms of its pathophysiology, epidemiology, risk factors, clinical presentation, and treatment strategies.

Background and objective: Headache disorders are ranked among the top 10 causes of disability worldwide and are notably prevalent within university student populations. This study aimed to (a) assess the prevalence of headaches and their impact among university students, (b) examine the correlation between headaches and dynamic balance, and (c) investigate the correlation between headaches and levels of physical activity.

Methods: The cross-sectional study was conducted at Universiti Tunku Abdul Rahman and involved 471 participants by using convenience sampling. A digital screening questionnaire was used to obtain demographic data and screen the participants. The Headache Impact Test (HIT-6) and the self-administered short International Physical Activity Questionnaire (IPAQ) Long Last 7 Days were conducted by eligible participants. Timed Up and Go (TUG) and Timed Up and Go Dual Task (TUG-DT; Cognitive and Manual) were assessed to measure dynamic balance.

Results: A 96.9% response rate was obtained in the study. The prevalence of headaches among university students was 44% (n = 208). Spearman correlation analysis indicated very weak to weak correlations that are not statistically significant between headache severity and physical activity levels (r = 0.064, p > 0.05), or with single-task dynamic balance (r = 0.118, p > 0.05) and manual dual-task balance (r = 0.183, p > 0.05). However, a significant positive correlation was observed between headache severity and cognitive dual-task balance performance (r = 0.292, p < 0.05), indicating that greater headache impact is associated with poorer balance under cognitive dual-task conditions.

Conclusions: Headache prevalence among university students was 44%, higher in females and younger individuals. While headache severity showed no significant correlation with physical activity or most dynamic balance measures, it was significantly associated with impaired balance under cognitive dual-task conditions, indicating a potential impact on motor-cognitive integration.

Neurons are especially vulnerable because of their high metabolic activity and limited ability to repair damaged DNA. Oxidative genotoxic stress (OGS), which arises from the buildup of short-lived, highly reactive molecules called reactive oxygen species (ROS), can damage neuronal DNA and compromise antioxidant defense mechanisms in neurons. OGS induces considerable forms of DNA damage, including genomic instability, DNA strand breaks (single or double), DNA base modifications such as 8-oxoguanine, and epigenetic changes, leading to compromised neuronal functions. Moreover, OGS is a silent player in mitochondrial DNA damage and mitochondrial dysfunction. Therefore, ROS-mediated OGS is pivotal for initiating and advancing several neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinsonism (PD), and Huntington's disease (HD). However, there is a significant gap in deciphering the molecular pathways involved in OGS-mediated development of neurodegenerative diseases. Hence, this study focused on the molecular mechanisms by which OGS causes neurodegeneration, with a focus on the contributions of neuroinflammation, mitochondrial dysfunction, and defective DNA repair pathways. Additionally, new therapeutic approaches, such as mitochondrial-targeted medications, antioxidant therapies, gene editing tools such as CRISPR/Cas9, and biomarkers for the early diagnosis of these oxidative diseases, have been assessed. A thorough comprehension of these processes opens exciting possibilities for focused treatments in neurodegenerative illnesses.

Major depressive disorder is one of the most burdensome mental health disorders. Probiotics have been shown to ameliorate depressive symptoms, though the mechanism remains unclear. This study was conducted to investigate whether extracellular vesicles (EVs) extracted from the probiotic beverage water kefir could influence gene and protein expression in human-derived neuroblastoma cells in vitro. EVs were extracted from lab-cultured water kefir and a control solution without water kefir grains by ultracentrifugation. Water kefir vesicles were imaged via electron microscopy. Neuroblastoma, microglia, and neuroblastoma-microglia co-cultures were exposed to water kefir EVs or negative control medium. Uptake of water kefir EVs was identified by microscopy. All conditions were quantified for brain derived neurotrophic factor, fractalkine, and synaptophysin RNA and protein. Data were analyzed using factorial ANOVAs with significance set at 0.05. Water kefir vesicles were taken up by neuroblastoma cells, and incubation in neuroblastoma-microglia co-culture resulted in significantly higher levels of fractalkine protein compared to media-only control (p = 0.029). To our knowledge, this is the first study to identify potential interactions between EVs derived from the probiotic beverage water kefir and human neuronal cells. Further research is needed to fully elucidate the role played by probiotic-derived EVs in human health.

Data suggests that the available therapeutic tools are still insufficient to deal with suicidality. Non-Invasive Brain Stimulation techniques (NIBS) have entered the recognized guidelines for therapies in psychiatry due to the advantages related to safety and tolerability. The purpose of this review and meta-analysis is to assess if and how NIBS techniques are used and could be effective in the treatment of suicidal ideation. The search included the Scopus, Pubmed, and Web of Science databases. The word "suicide" was combined with "NIBS", "transcranial magnetic stimulation" (TMS), "deep TMS" and "transcranial direct current stimulation". Nine studies met the inclusion criteria and were included in the review. High frequency repetitive TMS (rTMS) protocols were associated with a significant reduction in suicidal ideation, with individual studies reporting improvements ranging from 20% to over 35% on scales such as the scale for suicide ideation (SSI) and the Beck scale of suicide ideation (BSI) (p < 0.01; p < 0.01; p < 0.001). The meta-analysis showed that active rTMS significantly reduced suicidal ideation compared to sham control conditions (Z = 16.79, p < 0.0001). Heterogeneity was high (I² = 99%, chi-square = 473.22, df = 3, p < 0.0001). High frequency rTMS protocols appeared most effective; deep TMS (dTMS) showed mixed results, and only one study utilized transcranial direct current stimulation (tDCS). Due to limited data, no meta-analysis was conducted on dTMS or tDCS studies. Although preliminary findings suggest a potential for NIBS techniques to reduce suicidal ideation, the current evidence is limited by the small number of high-quality studies and heterogeneity in the protocols and outcomes. Therefore, conclusions regarding clinical efficacy should be considered tentative.

Dynamic knee valgus (DKV) is a prevalent risk factor for anterior cruciate ligament (ACL) injuries in soccer players, particularly during noncontact mechanisms. Transcranial direct-current stimulation (tDCS) and core stability exercises have shown promise in enhancing motor control and biomechanical alignment, but their combined effects on DKV remain unexplored. This study aimed to evaluate the efficacy of active versus sham tDCS combined with core stability exercises on knee kinematic alignment and lower limb performance in young male soccer players with DKV. In this double-blind, randomized controlled trial, 42 male soccer players (aged 18-25 years) with DKV were randomly assigned to either an active tDCS group (n = 21) or a sham tDCS group (n = 21). Both groups underwent 8 weeks of core stability exercises (3 sessions/week, 30 minutes/session) preceded by 15 minutes of active (2 mA) or sham tDCS targeting the primary motor cortex (M1). The primary outcome was the frontal plane projection angle (FPPA) during a single-leg landing task, measured using 2D video analysis. Secondary outcomes included vertical jump height and 8-hop test time. Outcomes were assessed at baseline and post-intervention. A 2 × 2 mixed-model ANOVA with Bonferroni-corrected post hoc tests was used for statistical analysis via SPSS₂₇. The active tDCS group showed significantly greater improvements in FPPA (+5.65% vs. +2.26%, p < 0.001, ηp² = 0.82), vertical jump height (+25.30% vs. +10.45%, p < 0.001, ηp² = 0.75), and 8-hop test time (-21.05% vs. -14.27%, p < 0.001, ηp² = 0.68) compared to the sham group. Both groups improved from baseline, but the active tDCS group exhibited larger effect sizes across all outcomes. Active tDCS combined with core stability exercises significantly enhanced knee kinematic alignment and lower limb performance in soccer players with DKV compared to sham tDCS. These findings suggest that neuromodulation, when paired with targeted exercise, is a promising strategy for injury prevention and performance enhancement in athletes. Further research is needed to explore long-term effects and applicability to diverse populations.

Facioscapulohumeral Muscular Dystrophy (FSHD) is a genetic disorder characterized by progressive muscle weakness, primarily affecting the facial, shoulder, and upper arm muscles. In this literature review, we examined the available treatments for FSHD, covering established methods and experimental approaches. We began with an overview of pharmacological treatments, emphasizing the importance of physical therapy and rehabilitation in maintaining muscle strength, improving mobility, preventing contractures, and respiratory therapy for severe cases. We also explored exercise interventions, addressing the debate surrounding exercise in FSHD patients, and highlight the possible benefits of aerobic and strength training, as well as ongoing research into safe exercise protocols. Additionally, the use of assistive devices and orthotics, such as braces and mobility aids, is discussed, along with surgical interventions like scapular fixation surgery and corrective procedures for foot drop. Emerging therapeutic strategies, including gene therapy focusing on DUX4 silencing and CRISPR-Cas9 technology, were evaluated. The potential of antisense oligonucleotides and myostatin inhibitors was reviewed, along with the challenges and ethical considerations associated with cell-based therapies. We aimed to inform researchers and advance treatment strategies for FSHD patients.

The calcium-dependent enzyme Transglutaminase 2 (TG2) (E.C. 2.3.2.13), which can promote post-translational modifications of proteins, is involved in several physiological processes, including development, neuronal cell death, and differentiation, as well as synaptic plasticity and transmission in the central nervous system (CNS). Several studies highlight the potential role of the TG2/NF-κB activation pathway in neurodegenerative diseases, including Multiple Sclerosis (MS), and the neuroinflammation that is associated with these conditions. The cross-linking activity of TG2, facilitating the formation of isopeptide bonds between glutamine and lysine residues, appears to be involved in forming protein aggregate deposits in these pathological conditions. Specifically, in the chronic neuroinflammation of MS, TG2 seems to play a central role in the fibrotic process of the lesion. Several potential biomarkers have been investigated for the prognosis and monitoring of MS, but no researchers have explored the presence of potential inflammatory signals in peripheral blood mononuclear cells (PBMCs) during the presymptomatic stage of MS, known as Radiologically Isolated Syndrome (RIS), on account of the lack of information regarding its pathological aspects. Since researchers have demonstrated a correlation between TG2 mRNA levels in PBMCs and the clinical and radiological progression of MS, we aimed to evaluate the expression levels of TG2 in RIS patients, comparing them with those in relapsing-remitting MS (RRMS) patients and healthy controls (HCs) using real-time PCR analysis. Preliminary data showed that RIS patients exhibit lower TG2 mRNA expression levels compared to RRMS patients, while no difference in TG2 mRNA expression being observed between RIS patients and HCs. This suggests that RIS patients exhibit a lower neuroinflammation grade than RRMS patients and that TG2 may represent a potential biochemical marker for assessing neuroinflammation associated with this disease. Future investigations may include longitudinal assessments of the potential role of TG2 mRNA blood levels in predicting or monitoring the progression from RIS to MS.

Although dopamine therapy is known to enhance creativity in some artists with Parkinson's disease (PD), similar creative changes have been observed in individuals with other neurological conditions, even without such treatment. This suggests that broader neurological and psychological factors beyond dopamine alone may influence creativity in PD. In this paper, I examined these influences through the lens of the 7 Muses of the Neuro-Creative Cycle: independence, curiosity, playfulness, confidence, openness, interdependence, and passion. Originally developed to support creativity in healthy individuals, the 7 Muses framework aligns closely with the structural and functional brain changes, as well as psychological shifts, commonly seen in PD. These changes may unlock latent creative potential, enabling PD artists to express themselves more authentically. By promoting a dynamic balance between top-down (goal-directed) and bottom-up (emotion-driven) processing across the creative cycle, preparation, imagination, and verification, PD-related changes may help reduce self-censorship, foster originality, and support the creation of meaningful, valuable work. Ultimately, beyond the effects of dopamine, some PD patients may awaken their dormant muses by following their intrinsic drives, listening more to their heart than their head.

COVID-19 vaccines have been effective in providing strong immunity within a relatively short time frame, significantly reducing both the severity of the disease and associated mortality. However, post-vaccination complications, particularly neurological disorders, have been reported. Among the more frequently documented neurological complications are acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), transverse myelitis (TM), optic neuritis (ON), Bell's palsy (BP), and Guillain-Barré syndrome (GBS). The precise role of COVID-19 vaccines in triggering the onset or relapse of these conditions remains uncertain. Immunological processes involving cytokines, chemokines, antibodies, and immune cells are believed to contribute to the pathogenesis of these neurological side effects. This review examines the immune responses triggered by COVID-19 vaccines and their potential role in the development of such complications. Despite reports of neurological side effects, these cases remain rare, and the overall benefits of vaccination in curbing the pandemic and preventing severe illness far exceed the risks. It is vital to sustain the progress of global vaccination efforts while continuously evaluating the risk-benefit ratio, particularly for individuals with underlying conditions. Ongoing research and surveillance are crucial for creating safer vaccines and identifying individuals who may be more susceptible to adverse reactions, ensuring broader protection against COVID-19.