Neuroscience
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Neuronal necroptosis and apoptosis are the most important pathways for programmed cell death after brain ischaemic stroke. Although apoptosis signalling pathways have been extensively studied, molecular mechanisms underlying necroptosis remain unclear. In this study, we found that receptor-interacting protein 3 (RIP3) deficiency reduced cerebral infarction volume, neurological deficits, and neuronal ultrastructural damage in a mouse model of brain ischaemic stroke by inhibiting programmed cell death. ⋯ We further confirmed that RIP3 deficiency inhibited the decrease of mitochondrial membrane potential, the increase of calcium influx and reactive oxygen species (ROS) production. In addition, compared with WT primary cortical neurons, the decreased expression of CaMKII and Pyk2 was further verified in a Ripk3-/- primary cortical neurons underlying oxygen and glucose deprivation/reoxygenation (OGD/R) model. In conclusion, we first identified that the RIP3/CaMKII/Pyk2 pathway is involved in programmed cell death after brain ischaemic stroke, which suggests it is a promising therapeutic target in ischaemia-induced neuronal injury.
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The prevalence of neurodegenerative disease has increased as an outcome of the aging population, and effective clinical treatments for such diseases are lacking. Endoplasmic reticulum dysfunction has been identified as a causative factor in various neurological disorders. ⋯ Herein, we focus on the multifaceted nature of IRE1α-XBP1 signaling and provide a detailed overview of the latest findings regarding its biological relevance in brain physiology and neurodegenerative disease pathobiology. Moreover, the possible pharmacological targets in the IRE1α-XBP1 axis are discussed.
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Depressive disorder is the leading cause of disability worldwide, yet the mechanisms underlying depression are not fully understood. Vesicle release is essential for synaptic neurotransmission, the abnormalities of vesicle release and synaptic plasticity are associated with various neuropsychiatric disorders. ⋯ To some extent, depression may be caused by a disruption in the structural and functional connections of the neural circuits underlying emotion regulation. In this review, we summarized the role of abnormalities of vesicle release and synaptic transmission, as well as the related regulatory molecules and signal pathways in the regulation of depression.
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Melatonin (MT) has been reported to control and prevent Alzheimer's disease (AD) in the clinic; however, the effect and mechanism of MT on AD have not been specifically described. Therefore, the main purpose of this meta-analysis was to explore the effect and mechanism of MT on AD models by studying behavioural indicators and pathological features. Seven databases were searched and 583 articles were retrieved. ⋯ Among the pathological features, subgroup analysis found that MT may ease the symptoms of AD mainly by reducing the deposition of Aβ40 and Aβ42 in the cortex. In addition, MT exerted a superior effect on ameliorating the learning ability of senescence-related and metabolic AD models, and corrected the memory deficit of the toxin-induced AD model. The study was registered at PROSPERO (CRD42021226594).
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We used the framework of the uncontrolled manifold hypothesis to explore force-stabilizing synergies and motor equivalence in the spaces of individual motor unit (MU) firing frequencies. Healthy subjects performed steady force production tasks by pressing with one finger or three fingers of a hand. Surface EMG was used to identify individual MU action potentials. ⋯ Effects of hand dominance were seen on multi-finger synergies but not intra-muscle synergies. We conclude that spinal mechanisms, such as recurrent inhibition and reflex loops from proprioceptors, contribute significantly to intra-muscle synergies, while multi-finger synergies reflect supra-spinal processes. These results provide methods to explore the contributions of spinal vs supraspinal circuitry to changed motor synergies in populations with a variety of neurological disorders.