Neuroscience
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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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Accumulating evidence suggests that neuroinflammation is the main mechanism in cognitive dysfunction and that brain-derived neurotrophic factor (BDNF) is involved in learning and memory by binding to tyrosine kinase B (TrkB) receptors. Herein, we tested the roles of the BDNF-TrkB signaling pathway and its downstream cascade in lipopolysaccharide (LPS) induced cognitive dysfunction in mice. Mice were treated with LPS (0.25 mg/kg) for 7 days, and learning and memory function was evaluated by the novel object recognition test (NORT). ⋯ In the entorhinal cortex, the protein levels of BDNF, p-TrkB, Bcl-2, p-CaMK2 and p-CREB were decreased, and the protein level of Bax was increased in LPS mice. Interestingly, 7,8-DHF alleviated these disorders in LPS mice and improved learning and memory function; however, the TrkB antagonist ANA12 effectively reversed effects of 7,8-DHF. Therefore, we conclude that the BDNF-TrkB signaling pathway and its downstream cascades disorders in different regions are main mechanisms of cognitive dysfunction, and 7,8-DHF maybe useful as a new treatment for preventing or treating cognitive dysfunction induced by neuroinflammation in neurodegenerative diseases.
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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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Genetic analyses have linked BTBD9 to restless legs syndrome (RLS) and sleep regulation. Btbd9 knockout mice show RLS-like motor restlessness. Previously, we found hyperactivity of cerebellar Purkinje cells (PCs) in Btbd9 knockout mice, which may contribute to the motor restlessness observed. ⋯ However, Syngap1 heterozygous knockout mice showed nocturnal, instead of diurnal, motor restlessness. Our results suggest that SYNGAP1 deficiency may not contribute directly to the RLS-like motor restlessness observed in Btbd9 knockout mice. Finally, we found that PC-specific Btbd9 knockout mice exhibited deficits in motor coordination and balance similar to Btbd9 knockout mice, suggesting that the motor effect of BTBD9 in PCs is cell-autonomous.