Neuroscience
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Vitamin D regulates multiple factors including those involved in the ontogeny of dopaminergic systems. It has been shown that in neonatal rats maternally deprived of vitamin D, dopamine (DA) turnover is decreased with associated reductions in one catabolic enzyme, catechol-o-methyl transferase (COMT). To directly examine this signaling relationship, in the present study we have over-expressed the vitamin D receptor (VDR) in neuroblastoma SH-SY5Y cells in order to examine the mechanisms by which the active vitamin D hormone, 1,25(OH)2D3, via its receptor VDR, affects DA production and turnover. ⋯ Chromatin immunoprecipitation revealed that 1,25(OH)2D3 increased VDR binding in three regions of the COMT promoter, strongly suggesting direct regulation. In addition, 1,25(OH)2D3 treatment attenuated increased levels of MAOA, DRD2 and VMAT2 gene expression caused by the VDR-overexpression. Taken together, these results show VDR and 1,25(OH)2D3 are directly involved in regulating the expression of dopaminergic-associated genes and that this in vitro neuronal model is a useful tool for identifying the role of 1,25(OH)2D3 in DA neuronal development and maturation.
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Small molecular G-protein plays a key role in several diseases. This study was designed to reveal the role of RhoA signaling in the pathophysiology of neuropathic pain in mice. Partial sciatic nerve injury caused thermal hyperalgesia, mechanical allodynia, and increased plasma membrane translocation of RhoA in the lumber spinal cord. ⋯ Pharmacological inhibition of ROCK also attenuated the increased expression of GFAP-ir and phosphorylated MARCKS-ir. Together, it is suggested that astrogliosis initiated by the activation of RhoA/ROCK signaling results in MARCKS phosphorylation in nerve terminals, which leads to hyperalgesia in neuropathic pain. Furthermore, simvastatin exerts antihyperalgesic and antiallodynic effects through the inhibition of spinal RhoA activation.
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Autism susceptibility candidate 2 (AUTS2) is a gene associated with autism and mental retardation. Recent studies have suggested an association of the AUTS2 gene with heroin dependence, and reduced AUTS2 gene expression may confer increased susceptibility to heroin dependence. However, the functional role of the AUTS2 protein in regulating enduring neuroadaptations in response to heroin exposure has not been established. ⋯ AUTS2 mRNA and protein expression in the NAc, but not the CPu, was decreased after chronic heroin (1mg/kg) administration. In the NAc, the expression of heroin-induced locomotor sensitization was enhanced through the lentiviral-AUTS2-shRNA-mediated knockdown of AUTS2, while the overexpression of AUTS2 attenuated the locomotor-stimulant effects of heroin. Together, these results indicate that AUTS2 in the NAc, but not the CPu, suppresses the initiation and expression of heroin-induced behavioral sensitization, suggesting that AUST2 may be a potential target for the treatment of heroin dependence.
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The bed nucleus of the stria terminalis (BST) plays an important role in integrating and relaying input information to other brain regions in response to stress. The cytoarchitecture of the BST in tree shrews (Tupaia belangeri chinensis) has been comprehensively described in our previous publications. However, the inputs to the BST have not been described in previous reports. ⋯ In addition, the different densities of BST-projecting neurons in various regions were analyzed in the tree shrew brains. In summary, whole-brain mapping of direct inputs to the BST is delineated in tree shrews. These brain circuits are implicated in the regulation of numerous physiological and behavioral processes including stress, reward, food intake, and arousal.
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Diazoxide, a well-known mitochondrial KATP channel opener with neuroprotective effects, has been proposed for the effective and safe treatment of neuroinflammation. To test whether diazoxide affects the neurogenesis associated with excitotoxicity in brain injury, we induced lesions by injecting excitotoxic N-methyl-d-aspartate (NMDA) into the rat hippocampus and analyzed the effects of a daily oral administration of diazoxide on the induced lesion. Specific glial and neuronal staining showed that NMDA elicited a strong glial reaction associated with progressive neuronal loss in the whole hippocampal formation. ⋯ Diazoxide treatment attenuated the NMDA-induced hippocampal injury in rats, as demonstrated by decreases in the size of the lesion, neuronal loss and microglial reaction. Diazoxide also increased the number of BrdU/NeuN double-stained cells and elevated the number of Sp8-positive cells in the lesioned hippocampus. These results indicate a role for KATP channel activation in regulating excitotoxicity-induced neurogenesis in brain injury.