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缺乏单胺氧化酶 B 的小鼠在给予安非他命后嗅球层中 GABA 能表达下调。

Down-regulated GABAergic expression in the olfactory bulb layers of the mouse deficient in monoamine oxidase B and administered with amphetamine.

机构信息

Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan, ROC.

出版信息

Cell Mol Neurobiol. 2010 May;30(4):511-9. doi: 10.1007/s10571-009-9475-2. Epub 2009 Nov 10.

DOI:10.1007/s10571-009-9475-2
PMID:19902350
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2875355/
Abstract

This study explores primarily the role of the activity of monoamine oxidase B (MAOB) in the regulation of glutamic acid decarboxylase(67) (GAD(67)) expression in distinct layers of main olfactory bulb (OlfB), which links the limbic system. Moreover, the response of GAD(67) was investigated to amphetamine perturbation in the absence of MAOB activity. Immunocytochemical analysis was performed on OlfB sections prepared from the adult wild type (WT) and the MAOB gene-knocked-out (KO) mice after receiving repeated intraperitoneal injections (two doses per day, total seven doses) of saline or amphetamine, 5 mg/kg. The levels of the GAD(67) immunoreactivity were approximate 25 and 38% lower in respective glomerular (GloL) and mitral cell layers (ML) of saline-treated KO mice than that of WT, whereas similar in the external plexiform or granule cell layers (GraL) of the KO and WT. In the GloL, the level of tyrosine hydroxylase was 39% lower in the KO mice than WT, implicating different dopamine content in the KO from WT. The amphetamine exposure down-regulated the levels of GAD(67) in the WT layers by 46 to 52%, and in KO layers 65 to 71%, except ML. The GraL GAD(67) level may be regulated by the activation of CREB, as the phosphorylated (p) CREB coexisted with GAD(67), and the percentage of GAD(67)-expressing pCREB neurons was decreased by the amphetamine exposure. The data indicate that the activity of MAOB could modulate the regular and amphetamine-perturbed expression of GAD(67) and pCREB. Thus, interactions are suggested among the MAOB activity, GABA content of OlfB, and olfaction.

摘要

本研究主要探讨了单胺氧化酶 B(MAOB)的活性在调节连接边缘系统的主要嗅觉球(OlfB)不同层谷氨酸脱羧酶(GAD(67))表达中的作用。此外,还研究了在没有 MAOB 活性的情况下,GAD(67)对安非他命的反应。在成年野生型(WT)和 MAOB 基因敲除(KO)小鼠接受重复腹腔注射(每天两次,共七次)盐水或安非他命(5mg/kg)后,对 OlfB 切片进行免疫细胞化学分析。与 WT 相比,分别接受盐水处理的 KO 小鼠的各自肾小球(GloL)和僧帽细胞层(ML)中的 GAD(67)免疫反应性水平低约 25%和 38%,而 KO 和 WT 的外丛状或颗粒细胞层(GraL)中的水平相似。在 GloL 中,KO 小鼠中的酪氨酸羟化酶水平比 WT 低 39%,表明 KO 中的多巴胺含量与 WT 不同。安非他命暴露使 WT 层中的 GAD(67)水平下调了 46%至 52%,而 KO 层中的 GAD(67)水平下调了 65%至 71%,除了 ML。GraL 的 GAD(67)水平可能受 CREB 的激活调节,因为磷酸化(p)CREB 与 GAD(67)共存,并且安非他命暴露使表达 GAD(67)的 pCREB 神经元的百分比减少。数据表明,MAOB 的活性可以调节 GAD(67)和 pCREB 的正常和安非他命干扰表达。因此,MAOB 活性、OlfB 的 GABA 含量和嗅觉之间存在相互作用。

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