Neuroscience
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White matter lesions are common when global cerebral ischemia (GCI) occurs in the elderly, and cause damage to neurological and psychological functions. Remyelination often fails because of the limited recruitment of oligodendrocyte progenitor cells (OPCs) to the demyelinated site or the inefficient differentiation of OPCs to mature oligodendrocytes (OLs). The activation of microglia, the most important immune cells in the central nervous system, and subsequent inflammation have been implicated in myelination repair disorder. ⋯ No effect was found on myelin in the corpus callosum. Besides, hippocampal neurons were protected by anti-FKR treatment after GCI. Collectively, our data demonstrated that downregulating of the Fractalkine/CX3CR1 signaling pathway had an anti-depressant and cognition-improvement effect by inhibiting microglia activation, promoting OPCs maturation and remyelination.
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Autism Spectrum Disorders (ASD) are caused by disrupted neurodevelopment leading to socio-communication and behavioural abnormalities. Although genetic anomalies like Copy Number Variations (CNV) have been implicated in ASD, their overall genomic landscape and pathogenicity remain elusive. Therefore, we created a CNV map for ASD using 9337 cases and 5650 controls from SFARI database, statistically marked genomic regions with high and low frequencies of CNVs (i.e., common and rare CNV regions respectively), performed gene function enrichment for CNV genes, built functional networks, pathways and examined their expression in brain tissues. ⋯ While common CNV regions were found in loci 15q11.2, 16p11.2, 22q11.21, 15q13.2-13.3, rare CNV regions in loci 4p16.3, 9q34.3, 7q11.23, 17p11.2 contributed significantly to protein interaction networks and were highly expressed in brain. Enriched CNV genes were clustered in six functional categories with either direct roles in neurodevelopment or auxiliary roles like cellular signalling via MAPK pathway, cytoskeletal organization and transport or immune regulation. Mechanisms through which these molecular systems could independently or in combination trigger an ASD phenotype were predicted.
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Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family, best characterized for its survival and differentiative effects in the central nervous system. Pro-BDNF, known as the precursor of BDNF, is believed to have opposite functions to mature BDNF (mBDNF). The opposing effects of Pro-BDNF and mBDNF have led researchers to propose a 'yin' (Pro-BDNF) and 'yang' (mBDNF) model of which, the specific mechanism of its opposing functions is unclear and requires further investigation. ⋯ Heterozygous (Het) mice showed impaired learning and memory capability and depressive-like behaviours, compared with wild type (WT) mice. Overall, these results support that pro-domain of BDNF is an indispensable part of the BDNF gene; without the proper formation of pro-BDNF, mBDNF cannot be produced successfully and function correctly on its own. Our study also supports the BDNF hypothesis in the pathogenesis of HD.
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The miRNA miR-124 has been reported to be a promising target for the repair of spinal cord injury (SCI), which is a devastating neurological condition. This study aimed to investigate the underlying molecular mechanisms of miR-124-mediated SCI repair. We established miR-124 SCI model rats and further treated them with agomiR-124 for 14 days. ⋯ In addition, we noted that Tal1 is a potential target gene of miR-124, and that a low level of this gene promoted the proliferation of neuronal precursor cells and inhibited their differentiation. In conclusion, miR-124 was able to mediate SCI repair by altering the expression of various mRNAs in rats. The miR-124/Tal1 axis may participate in the treatment of SCI by agomiR-124 by repopulating neural stem cells.
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Editorial Comment
The role of TGF-β1 in promoting microglial Aβ phagocytosis.