Neuroscience
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Elevated blood serotonin in perinatal development is the most consistent neurochemical finding reported in Autism Spectrum Disorder (ASD), and has been implicated in the pathogenesis of the disorder. Accordingly, pre- and postnatal administration of the non-selective serotonin agonist, 5-methoxytryptamine (5-MT), is hypothesized as a model of developmental hyperserotonemia (DHS) to investigate the behavioral and morphological implications in ASD. Our previous study, examining the effects of DHS, found significant neuroanatomical changes in the dendritic architecture and connectivity of neurons in the dentate nucleus of the cerebellum. ⋯ While results did not show a change in the overall volume of the thalamus, when grouped by estimated total brain volume, the mean thalamic volume was significantly reduced in the DHS group relative to controls. Additionally, significant reductions in cell numbers, density and distribution were observed in subdivisions of the principle nuclei including the ventral anterior, ventral lateral, ventral posterolateral, and ventral posteromedial nuclei. Alterations in these areas and their reciprocal connections throughout the brain may effect neuronal organization and be implicated in the neuropathological and behavioral changes observed in ASD.
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Pathological accumulation of tau protein in brain cells is the hallmark of a group of neurodegenerative diseases called tauopathies. Accumulation of tau protein begins years before the onset of symptoms, which include deficits in cognition, behavior and movement. The pre-symptomatic phase of tauopathy may be the best time to deliver disease-modifying treatments, but this is only possible if prognostic, pre-symptomatic biomarkers are identified. ⋯ Down-regulation of these microRNAs persisted at 53 weeks of age, when hTau mice exhibit cognitive deficits and advanced neuropathology. Bioinformatic analysis showed that these three microRNAs converge on pathways associated with neuronal signaling and phosphorylation of tau. Thus, these circulating microRNAs appear to reflect neuropathological change and are promising candidates in the development of biomarkers of pre-symptomatic tauopathy.
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Individuals continuously confronted with various stresses in modern life generate high levels of cortisol (corticosterone in rodents), the major glucocorticoid secreted by adrenal gland when hypothalamic-pituitary-adrenal axis is activated. Chronic stress can induce constant release of glucocorticoid and cause many serious health problems, such as mental disorders, cardiovascular diseases and autoimmune diseases. Many studies have suggested the neurotoxic effect of corticosterone is mediated through increased oxidative stress and apoptosis. ⋯ By utilizing a cellular stress model of exposing cells to corticosterone, our study found that there were a dose-dependent decrease in SIRT1 and an increase in LC3B II/I expressions with increasing concentrations of corticosterone. In combination with SIRT1 overexpression and knockdown plasmids, the regulation of SIRT1 expression in vitro demonstrated that SIRT can inhibit corticosterone-induced autophagy and enhance cell apoptosis. These findings might help us better understand the role of SIRT1 and autophagy activation in chronic stress.
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Angiopoietin (Ang) is an angiogenic factor, but its neuroprotective and neurotrophic effects have recently come to light. Ang exerts neuroprotective effects by inhibiting neuronal apoptosis, protecting the blood-brain/blood-spinal cord barrier, reducing inflammation and promoting neovascularization. ⋯ In addition, Ang and vascular endothelial growth factor (VEGF) are known to interact in blood vessels in the nervous system and the combination of Ang and VEGF can mitigate the negative effects of VEGF, such as inflammation and local edema. These data indicated that Ang is a novel neuroprotective/neurotrophic factor, which may become a new tool for the treatment of nerve injury.
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Parkinson disease (PD) is a leading neurodegenerative disease, with multifaceted interacting mechanisms. The Thy1-aSyn mouse model of PD exhibits many features of PD patients, including sensorimotor and olfactory dysfunction and protein aggregation. Here, we tested the hypothesis that the dipeptide carnosine, which has anti-aggregating and metal-chelating properties, would provide beneficial effects on the motor and olfactory deficits observed in Thy1-aSyn mice. ⋯ In contrast, intranasal carnosine prevented the normal decline in gait function seen in the challenging beam test in the Thy1-aSyn mice. Moreover, carnosine-treated Thy1-aSyn mice exhibited decreased aSyn immunostaining in the olfactory epithelium compared to vehicle-treated Thy1-aSyn mice, and the carnosine transporter Pept2 was immunolocalized to the apical surface of the olfactory epithelium. These findings demonstrate that intranasal carnosine shows promise in slowing the progression of motor deficits and aSyn deposition in PD.