Neuroscience
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In recent decades, our understanding of the molecular changes involved in neurodegenerative diseases has been transformed. Single-cell RNA sequencing and single-nucleus RNA sequencing technologies have been applied to provide cellular and molecular details of the brain at the single-cell level. This has expanded our knowledge of the central nervous system and provided insights into the molecular vulnerability of brain cell types and underlying mechanisms in neurodegenerative diseases. In this review, we highlight the recent advances and findings related to neurodegenerative diseases using these cutting-edge technologies.
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Review
The potential role of AMPA receptor trafficking in autism and other neurodevelopmental conditions.
Autism Spectrum Disorder (ASD) is a multifaceted condition associated with difficulties in social interaction and communication. It also shares several comorbidities with other neurodevelopmental conditions. Intensive research examining the molecular basis and characteristics of ASD has revealed an association with a large number and variety of low-penetrance genes. ⋯ Despite the high genetic heterogeneity in ASD, surface trafficking of the α-amino-3-hydroxy-5-Methyl-4-isoxazolepropionate (AMPA) receptor is a vulnerable pathway in ASD. In this review, we discuss autism-related alterations in the trafficking of AMPA receptors, whose surface density and composition at the post-synapse determine the strength of the excitatory connection between neurons. We highlight genes associated with neurodevelopmental conditions that share the autism comorbidity, including Fragile X syndrome, Rett Syndrome, and Tuberous Sclerosis, as well as the autism-risk genes NLGNs, IQSEC2, DOCK4, and STXBP5, all of which are involved in regulating AMPAR trafficking to the post-synaptic surface.
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Randomized Controlled Trial
Effect of High-definition Transcranial Direct Current Stimulation on Conditioned Pain Modulation in Healthy Adults: A Crossover Randomized Controlled Trial.
The disorder of the conditioned pain modulation (CPM) system is one of the main causes of pain perception in individuals. High-definition transcranial direct current stimulation (HD-tDCS) targeting specific brain areas was indicated to have an analgesic effect possibly by activating the endogenous pain inhibition pathway evident in CPM. However, discrepancies were found in previous limited studies of varied homogeneity and quality. ⋯ The changes of CPM were positively correlated with the total physical activity volume. In conclusion, our findings provide evidence support to the effectiveness of HD-tDCS on endogenous pain modulation among healthy adults. Further studies are required to explore the analgesic effect of tDCS among patients with chronic pain, thereby facilitating optimal chronic pain management.
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Deficiency in peroxisome proliferator-activated receptor gamma coactivator 1-alpha. (PGC-1α) expression or function is implicated in numerous neurological and psychiatric disorders. PGC-1α is required for the expression of genes involved in synchronous neurotransmitter release, axonal integrity, and metabolism, especially in parvalbumin-positive interneurons. As a transcriptional coactivator, PGC-1α requires transcription factors to specify cell-type-specific gene programs; while much is known about these factors in peripheral tissues, it is unclear if PGC-1α utilizes these same factors in neurons. ⋯ In ERRα null mice, PGC-1α-dependent genes were reduced in multiple regions, including neocortex, hippocampus, and cerebellum, though not to the extent observed in PGC-1α null mice. Behavioral assessment revealed ambulatory hyperactivity in response to amphetamine and impairments in sensorimotor gating without the overt motor impairment characteristic of PGC-1α null mice. These data suggest that ERRα is required for normal levels of expression of PGC-1α-dependent genes in neurons but that additional factors may be involved in their regulation.
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Transcription factors bind specific sequences upstream of the 5' end of their target genes to ensure proper spatiotemporal expression of the target gene. This study aims to demonstrate that the transcription factor SP2 regulates expression of the Ski gene, which has specific binding sites for SP2, and thus enables Ski to regulate astrocyte proliferation. The upstream regulation mechanism of astrocyte proliferation was explored to further regulate the formation of glial scar in specific time and space after spinal cord injury. ⋯ Finally, a dual luciferase reporter assay and Chromatin immunoprecipitation (ChIP) assay confirmed that the promoter region of Ski contained a specific SP2 binding site. This is the first that SP2 has been identified and confirmed to play an important role in astrocyte proliferation by regulating Ski expression. These results may help identify novel targets for the treatment of spinal cord injury.