Neuroscience最新文献

The literature on the effect of fatigue on motor learning is limited and marked by inconsistent findings. This scoping review aimed to explore the available knowledge on the effects of fatigue induced by physical and cognitive exertion on motor learning, and to compile and understand how it is studied. A comprehensive search strategy using relevant index terms and keywords was conducted across MEDLINE, EMBASE, SPORTDiscus, Web of Science, PsycINFO, CINAHL, ERIC, and Dissertations & Theses Global. Twenty-five studies met the inclusion criteria. The findings revealed considerable inconsistencies in how fatigue and motor learning were defined and measured. None of the studies examined the effect of fatigue induced by combined physical and cognitive exertion, and only 7 studies investigated fatigue induced by cognitive exertion. Acuity tasks were the most frequently used to assess motor learning, employed in 14 studies. Notably, all participants were between 16.5 and 31 years of age, and reporting of key demographic and physiological characteristics such as sex, gender, physical activity level, and body mass index was inconsistent or absent. This review highlights the need for comprehensive definitions of both fatigue and motor learning to improve consistency and reproducibility across studies. Given the limited research on the effects of fatigue induced by cognitive and combined physical and cognitive exertion, future studies should prioritize using these experimental manipulations. Also, future studies should diversify the motor learning tasks used in research to allow both direct and conceptual replication. Additionally, broader age ranges and comprehensive participant profiling should be prioritized.

Although upregulation of toll-like receptor 2 (TLR2) excessively activates pro-inflammatory microglia through Aβ peptides, it remains unclear whether TLR2 regulates neuronal pyroptosis via the NF-κB/NLRP3 pathway in Alzheimer's disease (AD). We assessed TLR2 expression in peripheral blood from clinical samples and employed SH-SY5Y cells for initial screening. AD pathology was simulated by Aβ_1-42 stimulation, and pathway regulatory relationships were dissected through TLR2 knockdown, NF-κB overexpression, and NLRP3 activation experiments. APP/PS1 mice were treated with sh-TLR2. Results demonstrated that high TLR2 expression activated the NF-κB/NLRP3 pathway and promoted pyroptosis, while TLR2 silencing suppressed Aβ_1-42-driven pyroptosis in SH-SY5Y cells by inhibiting this pathway. NF-κB overexpression or NLRP3 activation partially reversed the protective effect of TLR2 silencing. In vivo experiments confirmed the role of TLR2 knockdown in AD mice. Thus, this study revealed that TLR2 drives neuronal pyroptosis via the NF-κB/NLRP3 pathway, providing a novel therapeutic target for AD. These findings complements existing microglia-centered TLR2 research and broadens the understanding of neuroinflammatory regulation. However, SH-SY5Y cells differ from primary neurons in maturity, which may limit mechanistic extrapolation. Further validation in induced pluripotent stem cells-derived primary neurons or humanized mouse models will enhance the clinical translational potential of these findings._{1-421-421-42.}

The acquired toxicity of the familial amyotrophic lateral sclerosis (ALS)-associated mutant Zn-superoxide dismutase 1 (SOD1) protein has been implicated in motoneuron death, and cytosolic aggregates or inclusions have been observed in the cytoplasm of motoneurons, astrocytes, and neuronal axons but not in that of microglia. This study elucidates the mechanisms by which mutant SOD1 does not aggregate in and is cleared by microglia. We generated pcDNA3-Venus-tagged SOD1 constructs: wild-type SOD1 and mutant SOD1 were used as controls, and the A4V, D90A, and G93A SOD1 mutants were used as disease-related constructs; these plasmids were introduced into the Ra2 microglia line for subsequent evaluation. In spinal cords collected from postsymptomatic G93A mice, very little aggregation of the mutant SOD1 protein was detected in microglia, consistent with previous reports. Our new findings, which were based on immunohistochemical, Western blot, and enzyme immunoassay analyses, revealed that the protein expression of mutant SOD1 in microglia is significantly lower than that of wild-type SOD1. Furthermore, we observed the recovery of mutant SOD1 protein levels in autophagy suppression experiments and its colocalization with WDFY3, a selective autophagy-related protein. These in vitro results demonstrate that only the mutant SOD1 protein (i.e., not wild-type SOD1) is degraded by selective autophagy. Furthermore, we found that both wild-type and mutant SOD1 are secreted directly from microglia. These findings provide an opportunity to elucidate the precise mechanism through which microglia manage mutant SOD1 proteins during the pathological process of ALS and are likely to lead to improvements in ALS treatment strategies.