Neuroscience
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Despite the high prevalence of medicinal use and abuse of opioids, their neurobiology and mechanisms of action are not fully understood. Experimental (animal) models are critical for improving our understanding of opioid effects in vivo. ⋯ As many human brain diseases involve pain and aberrant reward, we also summarize zebrafish models relevant to opioid regulation of pain and addiction, including evidence of functional interplay between the opioid system and central dopaminergic and other neurotransmitter mechanisms. Additionally, we critically evaluate the limitations of zebrafish models for translational opioid research and emphasize their developing utility for improving our understanding of evolutionarily conserved mechanisms of pain-related, addictive, affective and other behaviors, as well as for fostering opioid-related drug discovery.
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Prepulse inhibition (PPI) can be modulated by both the Val158Met (rs4680) polymorphism of the Catechol-O-Methyltransferase (COMT) gene and the menstrual-cycle-related hormone fluctuations, each of which affects the subcortical/cortical dopamine metabolism. PPI can also be modulated by attention. The attentional modulation of PPI (AMPPI) is sensitive to psychoses. ⋯ However, the decreasing pattern was not overserved in either Met/Met-carrier or Met/Val-carrier participants. Thus, in healthy younger-adult females, PPIPSC and PPIPSS, but not the AMPPI, is vulnerable to changes of ovarian hormones, and the COMT Val158Met polymorphism also has a modulating effect on this menstrual-cycle-dependent PPI variation. In contrast, the AMPPI seems to be more steadily trait-based, less vulnerable to ovarian hormone fluctuations, and may be useful in assisting the diagnosis of schizophrenia in female adults.
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A significant level of genetic heterogeneity has been demonstrated in intellectual disability (ID). More than 700 genes have been identified in ID patients. To identify molecular pathways underlying this heterogeneity, we applied whole-transcriptome analysis using RNA-Seq in consanguineous families with ID. ⋯ FGFR2, but not SHTN1, was previously reported as an ID causing gene. Detailed gene ontology analyses identified pathways linked to tyrosine protein kinase, actin cytoskeleton, and axonogenesis to be affected in ID patients. The findings reported here provide new insights into the candidate genes and molecular pathways underling ID and highlight the key role of actin cytoskeleton in etiology of ID.
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The advance of nanotechnology in drug delivery systems has allowed central nervous system (CNS) accumulation of several anti-tumor agents with poor brain penetration but also lead to concerns about central neurotoxicity. Vincristine is commonly administered as an effective anti-brain tumor drug. It is known to act by interfering with microtubule dynamics, but models for detailed elucidation of its mechanism of neurotoxicity are limited. ⋯ Further analysis using the STRING database found that, both MMP10 and fibronectin bind with MMP9 experimentally, and text-mining indicated an interaction between MMP10 and fibronectin. Our organoid model system allowed quantitative investigation of the effects of vincristine treatment. Our findings indicated vincristine exhibited dose-dependent neurotoxicity, inhibited fibronectin, tubulin, and MMP10 expression in cerebral organoids.
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Accumulating evidence relates finger gnosis (also called finger sense or finger gnosia), the ability to identify and individuate fingers, to cognitive processing, particularly numerical cognition. Multiple studies have shown that finger gnosis scores correlate with or predict numerical skills in children. Neuropsychological cases as well as magnetic stimulation studies have also shown that finger agnosia (defects in finger gnosis) often co-occurs with cognitive impairments, including agraphia and acalculia. ⋯ We also found sex differences in how GMV is associated with finger gnosis. While females showed a more distributed and extensive set of frontal and parietal clusters, males showed two striatal clusters. This study provides the first findings on structural brain features that correlate with finger gnosis.