Neuroscience
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Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts multiple effects via B1 and B2 receptor activation. In the cardiovascular system, bradykinin has cardioprotective and vasodilator properties. We investigated the effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for the parasympathetic cardiac regulation. ⋯ BK produced a dose-dependent depolarization of nucleus ambiguus neurons, which was prevented by the B2 receptor antagonist. In vivo studies indicate that microinjection of BK into nucleus ambiguus elicited bradycardia in conscious rats via B2 receptors. In summary, in cardiac vagal neurons of nucleus ambiguus, BK activates B2 receptors promoting Ca2+ influx and Ca2+ release from endoplasmic reticulum, and membrane depolarization; these effects are translated in vivo by bradycardia.
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Minimal hepatic encephalopathy (MHE) is induced by elevated intracranial dopamine (DA). Glutamate (Glu) toxicity is known to be involved in many neurological disorders. In this study, we investigated whether DA increased Glu levels and collaborated with Glu to impair memory. ⋯ DA activated TAAR1 to downregulate EAAT2 and increase extracellular Glu levels in MHE. Additionally, DA together with Glu caused decreased production of neuronal BDNF/NT3 and memory impairment through the activation of CaN/NFAT signaling in MHE. From these findings, we conclude that DA increases Glu levels via interaction with TAAR1 and disruption of EAAT2 signaling in astrocytes, and DA interacting with TAAR1 and Glu interacting with AMPAR synergistically decreased the production of BDNF by activation of CaN/NFAT signaling to impair memory in MHE rats.
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Parkinson's disease is a debilitating neurodegenerative movement disorder, characterized by the progressive and selective loss of dopaminergic neurons located in the substantia nigra, leading to clinical motor symptoms. The factors involved in PD are rather multifaceted. There are many cellular pathways contributing to its neuro-pathogenesis, which include abnormal protein aggregation, impaired ubiquitin proteasome system, autophagy, and neuroinflammation. ⋯ Since they somewhat modulate many mRNA targets simultaneously, many cellular pathways may be affected by one individual miRNA. Moreover, miRNAs can stably circulate in cerebrospinal fluid and blood, and their expression pattern can reflect the molecular pathophysiology, thus making them promising biomarkers in PD diagnosis and prognosis. In this review, we will review the recent progress on miRNA's mechanism in PD pathogenesis and discuss the possibilities of miRNAs as PD molecular biomarkers.
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The capacity to identify unanticipated abnormal cues in a natural scene is vital for animal survival. Stimulus-specific adaptation (SSA) has been considered the neuronal correlate for deviance detection. There have been comprehensive assessments of SSA in the frequency domain along the ascending auditory pathway, but only little attention given to deviance detection in the spatial domain. ⋯ The variability in neuronal spatial discriminability among the TRN population was directly related to response difference (RD) but not variance; meanwhile, further analyses attributed higher spatial sensitivity at deviant locations to larger RD. Astonishingly, a significant correlation was found between the amount of adaptation and deviant discriminability. Collectively, our results suggest that adaptation facilitates rare location discrimination by sharpening the response gap between two locations.
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Several diseases are characterized by cognitive instability, which is amplified in the conditions of sleep deprivation (SD). Cognitive instability in SD can be examined by the number of lapses on the psychomotor vigilance test (PVT), which is considered to be a gold standard in the field. However, the number of PVT lapses widely range according to inter-individual differences, from apparent cognitive resistance to severe cognitive impairment. ⋯ Our results showed significant negative correlations between numbers of PVT lapses and FA in multiple WM tracts, with the FA variations in the superior longitudinal fasciculus and splenium of the corpus callosum accounting for nearly 37.5% of individual variability in PVT lapses. In addition, dichotomized analyses indicated that the resilient participants exhibited significantly higher FA values compared with the vulnerable participants. Together, these findings suggest that cognitive instability after SD was closely associated with individual differences in WM integrity.