Neuroscience
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Processes associated with human brain development and function are exceedingly complex, limiting our capacity to investigate disease status and potential treatment strategies in vitro. Recent advancements in human cerebral organoid systems-which replicate early stage neural tube formation, neuroepithelium differentiation, and whole-brain regional differentiation-have allowed researchers to generate more accurate models of brain development and disease. ⋯ In this review, we provide an overview of various neural differentiation technologies, as well as a critical analysis of their strengths and limitations. We primarily focus on the generation of three-dimensional brain organoid systems and their application in infectious disease modeling, high-throughput compound screening, and neurodevelopmental disease modeling.
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Astrocytes, the main non-neuronal cells in the brain, have significant roles in the maintenance and survival of neurons. Oxidative stress has been implicated in various neurodegenerative disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Myxobacteria produce a wide range of bioactive metabolites with notable structures and modes of action, which introduce them as potent natural product producers. ⋯ The overall results showed myxobacterial extracts, especially from the strains Archangium sp. UTMC 4070 and Cystobacter sp. UTMC 4073, were able to protect human primary astrocytes from oxidative stress.
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MicroRNAs have been reported to be an important pathophysiological factor in neuropathic pain. However, the potential mechanism through which miRNAs function in neuropathic pain remains unclear. The purpose of this study was to explore the potential role of mir-34c in neuropathic pain in a mouse model of chronic constriction injury (CCI). ⋯ We also demonstrated that miR-34c suppressed the expression of NLRP3 by directly binding the 3'-untranslated region. Overexpression of miR-34c decreased the protein levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in the spinal cord in CCI mice. Together, our results indicated that miR-34c may inhibit neuropathic pain development in CCI mice through inhibiting NLRP3-mediated neuroinflammation.
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The brain-derived neurotrophic factor (BDNF) is a key player in brain functions such as synaptic plasticity, stress, and behavior. Its gene structure in rodents contains 8 untranslated exons (I to VIII) whose expression is finely regulated and which spliced onto a common and unique translated exon IX. Altered Bdnf expression is associated with many pathologies such as depression, Alzheimer's disease and addiction. ⋯ Interestingly, EGR1 has been widely characterized as a regulator of brain plasticity. In conclusion, we deciphered a mechanism by which GR downregulates Bdnf expression, identifying a novel functional crosstalk between glucocorticoid pathways, immediate early growth response proteins and Bdnf. As all these factors are well-recognized germane for brain pathophysiology, these findings may have significant implications in neurosciences as well as in therapeutics.
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The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that modify extracellular matrix components and play crucial roles in development and numerous diseases. ADAMTS18 is a member of the ADAMTS family, and genome-wide association studies made an initial association of ADAMTS18 with white matter integrity in healthy people of 72-74 years old. However, the potential roles of ADAMTS18 in central nervous system remain unclear. ⋯ Behavioral tests showed that Adamts18 KO mice had reduced levels of depression-like behaviors compared to their wild-type (WT) littermates. The increased neurite formation could be attributed in part to reduced phosphorylation levels of the collapsin response mediator protein-2 (CRMP2) due to activation of the laminin/PI3K/AKT/GSK-3β signaling pathway. Our findings revealed a critical role of ADAMTS18 in neuronal morphogenesis and emotional control in mice.