Neuroscience
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Stress is an adaptive and coordinated response to endogenous or exogenous stressors that pose an unpleasant and aversive threat to an individual's homeostasis and wellbeing. Glucocorticoids, corticosterone (CORT) in rodents and cortisol in humans, are adrenal steroids which are released in response to stressful stimuli. Although they help individuals to cope with stress, their overexposure in animals has been implicated in hippocampal dysfunction and neuronal loss. ⋯ OT was unable to protect primary hippocampal neurons prepared from OTR KO mice from CORT-induced apoptosis. These results indicate that OT has inhibitory effects on CORT-induced neuronal death in primary hippocampal neurons via acting on OTR. The findings suggest a therapeutic potential of OT in the treatment of stress-related disorders.
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The aims of this study were to examine the levels of serum and exosomal miR-137, miR-155 and miR-223, three neuroinflammation-related miRNAs, in dementia patients and to explore the value of these miRNAs for the diagnosis and prognostic evaluation of dementia. Thirty-two patients with dementia were enrolled, and sixteen volunteers without dementia served as controls. Serum exosomes were isolated by precipitation with ExoQuick and characterized by western blotting, nanoparticle-tracking analysis and immunofluorescence microscopy. ⋯ The level of miR-223 was significantly correlated with Mini-Mental State Examination (MMSE) scores, Clinical Dementia Rating (CDR) scores, magnetic resonance spectroscopy (MRS) spectral ratios and serum concentrations of IL-1β, IL-6, TNF-α, and CRP. The diagnostic utility of exosomal miR-233 was evaluated by the area under the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was 0.875. This study suggests that serum exosomal miR-223 is a promising biomarker for diagnosing dementia and evaluating the progression of disease.
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Neural activity varies continually from moment to moment. Such temporal variability (TV) has been highlighted as a functionally specific brain property playing a fundamental role in cognition. We sought to investigate the mechanisms involved in TV changes between two basic behavioral states, namely having the eyes open (EO) or eyes closed (EC) in vivo in humans. ⋯ This reduction is correlated with an increase in energy consumption and with regional GABAA receptor density. This suggests that the modulation of TV by behavioral state involves an increase in overall neural activity that is related to an increased effect from GABAergic inhibition in addition to any excitatory changes. These findings contribute to our understanding of the mechanisms underlying activity variability in the human brain and its control.
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Activity-dependent transcription factors critically coordinate the gene expression program underlying memory formation. The tumor suppressor gene, MEN1, encodes a ubiquitously expressed transcription regulator required for synaptogenesis and synaptic plasticity in invertebrate and vertebrate central neurons. ⋯ In vivo knockdown of MEN1 prevented LTM formation and conditioning-induced changes in neuronal activity in the identified pacemaker neuron RPeD1. Our findings suggest the involvement of a new pathway in LTM consolidation that requires MEN1-mediated gene regulation.