Neuroscience
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Previous studies have shown that nitric oxide can induce cysteine S-nitrosylation of total protein in synaptosomes, suggesting that nitric oxide may contribute to the regulation of synaptic protein function. Vesicular neurotransmitter transporters pack neurotransmitters into synaptic vesicles and play an important role in neurotransmission. In the central nervous system, vesicular monoamine transporter 2 (VMAT2) is responsible for the uptake of monoamines, vesicular acetylcholine transporter (VAChT) is responsible for the uptake of acetylcholine, while vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) are responsible for the uptake of glutamate. ⋯ Using the biotin switch assay followed by avidin precipitation and immunoblotting we found that the nitric oxide donor nitrosoglutathione (GSNO) not only increased total cysteine S-nitrosylation, but also increased cysteine S-nitrosylation of VMAT2, VAChT, VGLUT1 and VGLUT2 in the mouse brain. Further, GSNO also decreased the vesicular uptake of [(3)H]dopamine, [(3)H]acetylcholine and [(3)H]glutamate. Our studies suggest that the cysteine S-nitrosylation may play an important role in the regulation of vesicular neurotransmitter transport.
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Infancy is a critical period for brain development. Emerging evidence indicates that stress experienced during that period can have long-term programming effects on the brain and behavior. However, whether different time periods represent different vulnerabilities to the programming of different neurobehavioral domains is not yet known. ⋯ ELS-early-treated animals exhibited an increase in nectin-1 expression in the dorsal hippocampus, and this increase was associated with the social deficits seen in these animals. Our findings highlight the relevance of developmental age on stress-induced long-term behavioral alterations. They also suggest potential links between early stress-induced alterations in hippocampal Gabrg2 expression and the developmental programming of anxiety and between changes in hippocampal nectin-1 expression and stress-induced social impairments.
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Bone marrow mesenchymal stem cells (BMSCs) transplantation can ameliorate cognitive impairment in chronic ischemic brain injury, but the underlying mechanism is poorly understood. It is considered that the hippocampus holds the capabilities of memory consolidation and spatial navigation, and the gamma amino butyric acid (GABA)ergic system plays an important role in the control of learning and memory processes. Herein, we investigated whether transplantation of BMSCs could improve cognitive impairment via regulating the hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion. ⋯ Our results showed that the 2VO model presented decreased capacities of learning and memory and down-regulated the expression of GABA, GAD67 or GABA(B)R1 in the hippocampal CA1 subfield in comparison to the sham group (P<0.05), while administration of BMSCs (experimental group) manifested increased performances of learning sessions and probe tasks, as well as up-regulated expression of GABA, GAD67 or GABA(B)R1 compared with the control group I (P<0.05). Collectively, these findings suggest that transplantation of BMSCs is capable of improving cognitive impairment via up-regulating the hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion. Hence, BMSCs transplantation could serve as an important tool for cell therapy in chronic cerebral hypoperfusion disorders.
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The role of serotonin7 (5-HT7) receptors in the regulation of depression is poorly understood, particularly in Parkinson's disease-associated depression. Here we examined whether 5-HT7 receptors in the prelimbic (PrL) sub-region of the ventral medial prefrontal cortex (mPFC) involve in the regulation of depressive-like behaviors in sham-operated rats and rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. The lesion induced depressive-like responses as measured by the sucrose preference and forced swim tests when compared to sham-operated rats. ⋯ However, the doses producing these effects in the lesioned rats were higher than those in sham-operated rats. Neurochemical results showed that intra-PrL injection of AS19 (2 μg/rat) increased dopamine, 5-hydroxytryptamine (5-HT) and noradrenaline (NA) levels in the mPFC, habenula and ventral hippocampus (vHip) in sham-operated and the lesioned rats; whereas SB269970 (6 μg/rat) decreased 5-HT levels in the habenula and vHip, and the levels of NA in the mPFC, habenula and vHip in the two groups of rats. The results suggest that 5-HT7 receptors in the PrL play an important role in the regulation of these behaviors, which attribute to changes in monoamine levels in the limbic and limbic-related brain regions after activation and blockade of 5-HT7 receptors.
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Mitochondrial fission is predominantly controlled by the activity of dynamin-related protein1 (Drp1), which has been reported to be involved in mitochondria apoptosis pathways. However, the role of Drp1 in a rat model of cardiac arrest remains unknown. ⋯ Moreover, the increase of the vital neuron and the reduction of cytochrome c (CytC) release, apoptosis-inducing factor (AIF) translocation and caspase-3 activation in the brain indicate that this protection might result from the suppression of neuron apoptosis. Altogether, these results indicated that Drp1 is activated after cardiac arrest and the inhibition of Drp1 is protective against cerebral ischemic injury in a rat of cardiac arrest model via inhibition of the mitochondrial apoptosis pathway.