Search Results (341)

Microplastics (MPs) are emerging pollutants widespread in aquatic environments; however, their effects across the different life stages of aquatic organisms remain poorly understood. This systematic review integrates recent experimental results on the developmental, physiological, and neurobehavioral effects of MP exposure on zebrafish (Danio rerio), a popular model organism for ecotoxicology research. A PRISMA-guided search using Web of Science (WoS) and Scopus as databases generated 581 articles, which were screened to 60 eligible articles. The collated results showed that MP toxicity at various life stages of zebrafish was strongly related to the physicochemical properties of MPs and exposure conditions. In terms of developmental toxicity, peer-reviewed publications assessing specific MP physicochemical properties—polymer type, size, concentration, shape, and degree of aging—reported concentration-dependent effects, with increasing MP concentrations generally associated with growth inhibition, cardiac dysfunction, increased malformations, and lower hatching rate, particularly at ≥10 mg/L to ≥100 mg/L. However, several studies noted that under particle-based exposure scenarios, MP toxicity exhibited threshold-like or non-monotonic responses, attributed to aggregation, bioavailability, and uptake dynamics. Weathered and artificially aged MPs exhibited higher embryotoxicity and neurodevelopmental toxicity, including changes in gene expression of neurons, decreased integrity of motor neurons, and impaired retinal development, compared with “virgin” MPs. In terms of physiological endpoints, oxidative imbalance like changes in the activity of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)), lipid peroxidation, inflammation, and disruption of tight junctions have been reported as key toxicity pathways. Chronic MP exposure in zebrafish also caused changes in the gut microbiota, hepatic metabolism, endocrine disruption, reproductive damage, thyroid function disruption, and genotoxicity in zebrafish. In terms of neurobehavioral effects, changes in locomotor activity, anxiety response, neurotransmitter homeostasis, and acetylcholinesterase function, have been observed, in both larvae and adults, with a potentiation effect in aged MP exposure. Finally, this systematic review found major limitations for inter-study comparisons because of inconsistencies and differences in methodology applied related to MP concentration, simulation of natural MP aging, and MP dose measurements. Full article

Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disorder caused predominantly by homozygous deletion of SMN1, resulting in degeneration of lower motor neurons and progressive muscle weakness and atrophy. In recent years, newborn screening programs for SMA using dried blood spots and PCR-based assays have been introduced in several countries, enabling presymptomatic diagnosis and earlier initiation of therapy. However, newborn screening does not eliminate the need for diagnostic testing in routine clinical practice, because adolescents and adults with milder or ambulant phenotypes may still present only after symptom onset and may experience diagnostic delay. We therefore developed a single-tube nested PCR (STNPCR) method as a practical diagnostic approach for symptomatic patients with suspected SMA. This method enables detection of homozygous SMN1 deletions using only standard PCR procedures and gel electrophoresis and may help identify patients with SMA who are not captured by newborn screening. Our assay using dried blood spot samples demonstrated preliminary technical feasibility in this proof-of-concept cohort, although further validation in larger independent cohorts will be required before its diagnostic utility can be established. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by the selective degeneration of upper and lower motor neurons (MNs). Although the specific pathogenesis of ALS is not yet fully understood, there is increasing evidence that abnormal energy metabolism plays a key role in the onset and progression of the disease. Lactate has traditionally been considered a metabolic by-product of glycolysis and has received increasing attention in recent years. Research has shown that lactate is not only an important energy substrate but also a signaling molecule that regulates a variety of physiological processes, including neuron-glia metabolic coupling, neuroprotection and inflammatory responses. In ALS, abnormalities in lactate metabolism, dysfunction of the lactate shuttle, and dysregulation of lactate-related signaling pathways may jointly lead to neuronal energy deficits and increased neuroinflammation, thereby promoting MN degeneration. This review summarizes the latest advances in lactate metabolism and lactate-mediated signaling in ALS, with particular emphasis on their roles in neuronal energy regulation, neuroprotection and inflammatory regulation. In addition, we also discuss potential therapeutic strategies for lactate metabolism and its related pathways, aiming to provide new insights into the pathogenesis of ALS and the development of treatment methods for lactate-related metabolism. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by rapid motoneuron degeneration. Hydrogen sulfide (H₂S), a signaling molecule that regulates post-translational modification, has recently been implicated in the pathophysiology of ALS. Our study aimed to design, synthesize, and investigate the potential effects of (2S)-2-aminopentanethioic S-acid (POM16), an isomer of the slow-releasing H₂S donor thiovaline, in a genetic ALS model. FUS [1-359]-tg mice, which recapitulate ALS syndrome, and their wild-type (WT) littermates received POM16 (at a dose of 50/mg/kg) or standard ALS therapy riluzole (at a dose of 8 mg/kg/day) dissolved in drinking water, or vehicle, for six weeks starting at nine weeks of age. The onset of paralysis, physiological and motor functions, muscle atrophy, density of spinal cord motoneurons, gene expression of proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor (TNF), and concentration of oxidative stress marker malondialdehyde (MDA) in the spinal cord were studied. POM16-treated mutants displayed significant improvements in body weight, water and diet intake, as well as behavior in the rotarod, wire, and pole tests. The percentage of mice with paralysis on the 6th week of dosing was reduced from 48% in vehicle-treated mutants to 16% in POM16-treated FUS [1-359]-tg mice, while in the riluzole-treated group, it was 38%, not reaching significance. Notably, muscle weight was not significantly improved by the latter treatment, unlike the dosing with POM16. In comparison with vehicle-treated FUS [1-359]-tg mice, POM16-treated mutants had significantly higher motor neuron density in the spinal cord, lower MDA levels, and reduced muscle atrophy ranking. Thus, new compound POM16 has a therapeutic potential to counteract ALS pathology that is likely mediated via anti-oxidative stress mechanisms. Given that any effective treatment of this devastating disease is currently lacking, it is hoped that POM16 can be a promising therapy for ALS. Full article

Background/Objectives: Diabetes mellitus is known to exacerbate neural degeneration and impair regenerative capacity following injury. This study aimed to investigate the effects of Garcinia kola and curcumin on spinal cord morphology and neural structure in a diabetic sciatic nerve injury model. Methods: Spinal cord tissues were obtained from male Wistar albino rats subjected to sciatic nerve transection and diabetes induction in a previously established experimental model. Animals had been assigned to five experimental groups (n = 7 per group): control group, transected sciatic nerve group, transected sciatic nerve + diabetes mellitus (DM), transected sciatic nerve + diabetes mellitus + curcumin (DM + Cur), and transected sciatic nerve + diabetes mellitus + Garcinia kola (DM + GK). Curcumin (300 mg/kg/day) and Garcinia kola (200 mg/kg/day) were administered orally. All animals were sacrificed at three months post-injury. Cervical (C3–C5) spinal cord segments were processed for histological evaluation, and quantitative assessments were performed using unbiased stereological methods to estimate neuronal and structural parameters. Microscopic analyses were conducted to assess morphological alterations. Results: Diabetes combined with sciatic nerve transection induced marked structural alterations in the spinal cord, including reductions in neuronal density and disruption of tissue organization. The DM group showed a significantly lower number of motor neurons than the other groups; similarly, it showed a significant decrease in soma area compared to the Cont and Sham groups. Conclusions: Both the curcumin and Garcinia kola treatment groups exhibited partial preservation of spinal cord morphology. This study provides evidence that Garcinia kola and curcumin exert protective effects not only at the peripheral nerve level, but also in the spinal cord following diabetic nerve injury. Full article

Background/Objectives: Spinal cord epidural stimulation (scES) holds significant potential for restoring autonomic function after chronic spinal cord injury (SCI). A significant and often debilitating sequela of SCI is neurogenic lower urinary tract dysfunction, characterized by loss of voluntary bladder control, which adversely impacts patients’ dignity, urological health, and overall quality of life. In a pilot study of three individuals with SCI, an epidural electrode array was implanted between L2 and sacral segments to modulate lower urinary tract function for efficient emptying. Methods: Three participants with chronic thoracic clinically complete SCI were implanted with an epidural stimulator over the lumbosacral spinal cord. Array placement was confirmed using intraoperative and postoperative spatiotemporal mapping of known motor neuron pools following published protocols. In a controlled laboratory mapping, bladder storage and voiding neural networks were targeted during filling cystometry by interactively optimizing lower urinary tract stimulation parameters (electrode configuration, frequency, intensity, and pulse width). Efficacy was assessed during six-hour laboratory sessions of natural bladder filling, followed by approximately four months of daily at-home use. Results: Pre-implant cystometry revealed poor voiding efficiency and absent bladder sensation. Following bladder scES mapping and home training, one of the three participants regained direct bladder sensation, exceeded the 90% clinical threshold for efficient voiding, and continues to use scES for bladder management instead of intermittent catheterization, with no urinary tract infections reported since completion of training (February 2022). The inability of two participants to attain high voiding efficiency may be due to suboptimal adherence to prescribed bladder training protocols in one case and the presence of an elevated bladder neck in the other. All three participants reported off-target improvements in bowel and sexual functions. Conclusions: The present novel pilot study provides the first evidence supporting the potential use of epidural stimulation for bladder management and the importance of activity-based recovery training for durable performance. Full article

Peripheral facial palsy is often attributed to idiopathic Bell’s palsy, but secondary structural causes should be considered when local red flags are present. A 61-year-old man with a 40-pack-year smoking history and former betel quid chewing presented with a verrucous-appearing mass involving the left oral commissure and buccal mucosa, intermittent purulent discharge from the lesion, progressive left facial swelling, and ipsilateral lower-motor-neuron facial palsy with lagophthalmos. Magnetic resonance imaging demonstrated a left buccal/oral-cavity lesion with ipsilateral parotid duct obstruction. He underwent tracheostomy, wide excision, left supraomohyoid neck dissection, and radial forearm free-flap reconstruction. Pathology confirmed squamous cell carcinoma, pT2N0, cM0 (stage II), with perineural invasion; surgical margins were negative, and lymphovascular invasion was not identified. At follow-up, wound healing was satisfactory and purulent discharge had resolved, but lower-motor-neuron facial palsy persisted; adjuvant radiotherapy was recommended. This case emphasizes that lower-motor-neuron facial palsy with an oral mass, purulent discharge, facial swelling, or salivary-duct obstruction should prompt careful oral examination and head-and-neck imaging. Full article

Background/Objectives: Spinal muscular atrophy (SMA) types 2 and 3 are increasingly recognised as potentially multisystem disorders that may involve the central nervous system. However, the extent and pattern of brain structural alterations in adults remain insufficiently characterised. This study aimed to assess brain morphology in adult patients with SMA using Computational Anatomy Toolbox 12 (CAT12)-derived region-based morphometry and surface-based morphometry. Methods: The study included 27 right-handed adult patients with SMA types 2 and 3 and 27 age- and sex-matched healthy controls. MRI examinations were performed before initiation of disease-modifying therapy or during the early loading phase of intrathecal nusinersen treatment, with a maximum exposure of two months and no more than three doses before MRI. The groups did not differ significantly in age, sex distribution, or total intracranial volume. Regional volumetric measures and cortical surface-based parameters were extracted from predefined atlas-based regions of interest. Between-group differences and associations with selected clinical and genetic variables were analysed. p-values were corrected for multiple comparisons using the Benjamini–Hochberg false discovery rate procedure. Results: CAT12-derived region-based morphometry showed a significant reduction in grey matter volume in the left thalamus in patients with SMA compared with healthy controls. Surface-based morphometry revealed increased sulcal depth in the left orbital sulcus as the only cortical finding that remained significant after correction for multiple comparisons. Additional differences in cortical thickness and sulcal depth were observed only at nominal or exploratory thresholds and did not survive correction for multiple comparisons. Conclusions: Adults with SMA types 2 and 3 showed selected brain structural alterations, particularly reduced grey matter volume in the left thalamus and increased sulcal depth in the left orbital sulcus. These findings are consistent with the concept that SMA may extend beyond lower motor neuron degeneration. Larger longitudinal multimodal studies are warranted to validate these observations and clarify their clinical significance. Full article

Spasticity is a common and disabling consequence of upper motor neuron lesions, and its follow-up relies largely on clinical scales that may not fully reflect daily-life mobility. This prospective single-arm exploratory pilot study examined wearable-derived daily-life mobility metrics around a scheduled botulinum neurotoxin type A (BoNT-A) injection cycle and assessed their associations with established clinical measures. Thirteen patients with focal spasticity secondary to stroke (n = 11) or multiple sclerosis (n = 2) underwent baseline and 6-week follow-up assessment using the Modified Ashworth Scale (MAS), Motricity Index (MI), the Timed Up and Go test (TUG) and a multi-sensor wearable monitoring system. Device-derived outcomes included gait impairment, gait speed, stride length, angular velocity, and lack of movement. Clinical scales generally changed in the expected post-treatment direction, with reduced MAS scores and descriptive or directional improvements in MI scores and TUG performance. Wearable metrics captured descriptive changes in daily mobility, notably a reduction in lack of movement. Furthermore, in exploratory pooled analyses, selected gait-related metrics tended to be associated with TUG performance and lower-extremity MAS. These findings highlight the potential of wearable telemonitoring to complement conventional clinical scales by providing objective, real-world data, supporting its further validation as a tool for longitudinal spasticity management and neurorehabilitation. These device-derived metrics should be interpreted as mobility-related digital biomarkers rather than direct surrogate measures of spasticity. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons. While monogenic causes account for a minority of cases, in most cases, ALS is sporadic and likely arises from multilayer interactions of genetic architecture, aging-associated loss of genome regulation, and inflammatory stress. Long interspersed nuclear element-1 (LINE-1) retrotransposons are endogenous mobile elements that are tightly controlled through various cellular mechanisms under normal conditions. When abnormally active, they are involved in gene inactivation, expression regulation, and genomic instability, leading to cellular processes such as innate immunity and cell death. Here, we present mechanistic links between LINE-1 and ALS. These include evidence that the burden of retrotransposition-competent LINE-1s (RC-L1s) is increased in ALS genomes, positioning RC-L1 load as a candidate contributor to missing heritability in sporadic disease. We also integrate emerging data showing that LINE-1 RNA can be intrinsically toxic independently of new insertions, as it promotes chromatin opening and transcriptional epigenetic noise, particularly when nuclear RNA surveillance pathways fail in TDP-43 pathology. Finally, we review how LINE-1-derived DNA/RNA intermediates can engage innate immune sensors, highlighting the cGAS–STING axis as a plausible route from LINE-1 de-repression to neuroinflammation. Together, these concepts support a model in which genetic RC-L1 load and age-/pathology-driven LINE-1 de-repression converge on nuclear dysfunction and inflammatory amplification, suggesting concrete molecular nodes for therapeutic intervention. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease primarily affecting upper and lower motor neurons. Although cerebrovascular disease (CVD) and ALS have traditionally been studied as distinct entities, a growing body of evidence indicates meaningful epidemiological, pathophysiological, and clinical overlap between the two conditions. This narrative review synthesizes current evidence on the coexistence of ALS and cerebrovascular disease, examines shared mechanistic pathways, addresses diagnostic challenges, including stroke mimicry, considers clinical management implications, and identifies priorities for future research. A search of PubMed, Scopus, Web of Science, and EMBASE was conducted through February 2026 using the terms “amyotrophic lateral sclerosis,” “motor neuron disease,” “cerebrovascular disease,” “stroke,” “ischemic stroke,” “blood-brain barrier,” “neuroinflammation,” and “neurovascular coupling,” alone and in combination. Peer-reviewed original research, systematic reviews, meta-analyses, population-based studies, registry analyses, and expert consensus statements were included. Studies were assessed for methodological quality and relevance to the review objectives. This review is reported as a narrative synthesis. Population-based data demonstrate a bidirectional relationship between ALS and cerebrovascular events. ALS patients face an approximately 2.6-fold elevated risk of ischemic stroke, and prior cerebrovascular injury modestly increases subsequent ALS risk. Shared pathophysiological mechanisms include neuroinflammation with microglial M1/M2 polarization imbalance, pro-inflammatory cytokine cascades mediated via NF-κB signaling, oxidative stress and SOD1 pathway dysregulation, glutamate excitotoxicity, blood–brain barrier (BBB) dysfunction, and impaired neurovascular coupling. Diagnostic confusion arises because upper motor neuron–predominant ALS can closely mimic acute ischemic stroke. Concurrent cerebrovascular disease appears to accelerate functional decline and reduce survival in ALS. Resource-limited settings face compounded challenges from diagnostic misclassification, restricted EMG access, and limited specialist availability. The ALS–cerebrovascular overlap is clinically relevant, biologically plausible, and systematically understudied. Integrated multidisciplinary management, prospective longitudinal cohort studies, and linked registry analyses are urgently needed to clarify causal relationships, characterize shared disease mechanisms, and improve patient outcomes. Full article

Levodopa-induced dyskinesia (LID) is a severe motor complication associated with long-term levodopa (L-DOPA) treatment for Parkinson’s disease (PD). Its underlying mechanisms remain unclear, and candidate biomarkers lack consistency. To investigate cortico-striatal network alterations associated with LID, we simultaneously recorded single-neuron spikes and local field potentials (LFPs) from the dorsolateral striatum (DLS) and the primary motor cortex (M1) in LID rats. Our results showed that in the DLS, the LID group had a greater number of putative fast-spiking interneurons (FSIs) with lower firing rates, and fewer putative medium spiny neurons (MSNs) with higher firing rates. In M1, pyramidal neurons were fewer but fired faster, while interneurons were more numerous with no change in firing rate. Although gamma power increased and delta power decreased in both regions in LID rats, delta-gamma phase-amplitude coupling (PAC) was present in the DLS but absent in M1. Furthermore, cross-regional PAC analysis revealed significantly stronger coupling between the low-frequency phase of M1 and the high-frequency amplitude of the DLS than in the opposite direction, indicating an asymmetric pattern of cortico-striatal coupling in LID. These findings demonstrate region-specific alterations in neuronal activity and oscillatory coupling associated with LID and suggest that asymmetric cortico-striatal PAC may serve as a promising electrophysiological marker for characterizing abnormal network dynamics underlying dyskinesia. Full article

Background/Objectives: Presynaptic terminals (PTs) in the neuromuscular junction (NMJ) are essential regulators of skeletal muscle function and are responsible for the translation of electrical impulses from motor neurons into muscle contraction. The present exploratory study aimed to compare PT adaptations in spinalis muscle samples from the concave and convex regions of the spine in three cases of advanced scoliosis, which exhibited marked asymmetry in muscle development. Methods: Spinalis muscle sample pairs were retrieved after surgical procedures and subjected to immunofluorescence (IF)-based spatial analysis of PTs, histological assessment of muscle fibers, and expression analyses of inflammatory and neurotrophic proteins. Results: IF images revealed distinct differences in PT parameters between spinalis samples obtained from the corresponding concave and convex sides of spinal deformities. Advanced statistical models revealed a consistent tendency for concave spinalis muscles to develop lower PT numbers, along with decreased expression of relevant components, neurofilament M, and synaptic vesicle glycoprotein 2. Moreover, these impairments were accompanied by increased expression levels of IFN alpha, which has been previously implicated in NMJ disorders, neuropathies, and myopathies. Conclusions: In the concave regions of spinal deformities, continuously compressed spinalis muscles may be particularly susceptible to PT alteration and denervation. However, comprehensive multicenter validation studies are required to better define the relationships among PT alterations, IFN alpha expression, and muscle tissue compression. Full article

The vagus nerve (innervating the gut from esophagus to proximal colon) and sacral nerve (innervating distal colon and rectum) are key parasympathetic regulators of gastrointestinal (GI) function. While vagus nerve stimulation (VNS) has shown therapeutic potential in upper GI disorders, its role in modulating distal colon and rectal function remains poorly understood. This study investigated the effects and mechanisms of VNS on distal colon transit and rectal tone in rats. Adult male Sprague Dawley rats were implanted with stimulation electrodes at the cervical or auricular vagal afferent nerve. VNS was applied with varying frequencies, pulse widths, and amplitudes. Rectal tone was assessed using a barostat device, and distal colon transit was evaluated using bead expulsion. Nitrergic and cholinergic contributions were examined using L-NAME and nNOS expression, and acetylcholine ELISA and ChAT expression, respectively. Central pathways were investigated by immunofluorescence staining of c-fos and ChAT in the nucleus tractus solitarius (NTS). Sacral efferent pathway was assessed by chemogenetic inhibition of the dorsal motor nucleus of the vagus (DMV) and Barrington nucleus (BN/PMC). VNS (5 Hz, 0.1 and 0.5 ms, 0.5 mA) significantly increased rectal volume, indicating relaxation, and accelerated distal colon transit. L-NAME abolished VNS-induced rectal relaxation, while nNOS expression in the rectum was upregulated, confirming nitrergic mediation. Distal colon transit was associated with increased acetylcholine release and ChAT expression, highlighting cholinergic involvement. VNS enhanced c-fos and ChAT-positive neurons in the NTS, suggesting central integration of vagal afferent signals. Chemogenetic inhibition of DMV and BN attenuated rectal relaxation, indicating that VNS effects are mediated via a vagal–NTS–sacral pathway. VNS modulates distal colon transit and rectal tone through coordinated nitrergic and cholinergic signaling and central vagal-to-sacral circuits. These findings reveal functional crosstalk between vagal and sacral parasympathetic pathways and provide mechanistic insight into potential VNS therapy for lower GI disorders. Full article

Background: Spiking neural networks (SNNs) have attracted significant attention in the field of brain–computer interfaces owing to their distinctive biological plausibility and energy efficiency advantages. However, the discrete nature of spikes renders gradient-based differentiation infeasible, making it difficult to directly obtain well-trained SNNs. A common approach is to transfer the weights from artificial neural networks (ANNs) to SNNs. However, this process introduces conversion errors that pose significant challenges. Methods: To address these challenges, we propose the self-rectifying integrate-and-fire (SRIF) neuron, which employs negative spikes to reduce asynchronism error and rectification spikes to diminish clipping error. Concomitantly, we propose a collaborative trim (CT) training framework that introduces a quantized network to perceive the weights and results of SNNs, which can further improve performance. Result: The proposed training methodology enables SNNs to achieve performance metrics comparable to those of ANNs in EEG-based motor imagery (MI) classification. Conclusions: Experimental results demonstrate that our method not only preserves the superior classification performance of ANNs but also leverages the superior energy efficiency and lower computational complexity of SNNs. Full article