Alterations of BDNF and NT-3 genes expression in the nucleus paragigantocellularis during morphine dependency and withdrawal
Alterations of BDNF and NT-3 genes expression in the nucleus paragigantocellularis during morphine dependency and withdrawal
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DOI：
10.1016/j.npep.2007.04.007
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发表时间：
2007-10-01
期刊：
影响因子：
2.9
通讯作者：
Ahmadiani, Abolhassan
中科院分区：
文献类型：
--
作者：
Hatami, Homeira;Oryan, Shahrbanoo;Ahmadiani, Abolhassan
蓝斑（Locus coeruleus，LC）在阿片类药物依赖和戒断过程中起关键作用。慢性吗啡给药诱导去甲肾上腺素能系统的神经化学适应。负责阿片类药物诱导的适应性去甲肾上腺素能神经元在LC的信号的性质是没有很好的定义。脑源性神经营养因子（BDNF）和神经营养因子-3（NT-3）等神经营养因子信号通路在调节LC神经元对阿片类药物的去甲肾上腺素能反应中起关键作用。旁巨细胞核（PGi）是LC的两个主要传入纤维之一。本研究旨在评估BDNF和NT-3在阿片依赖和戒断PGi的背景下的表达。这些数据是重要的，因为它们可以揭示PGi作为BDNF和NT-3的额外来源在LC神经元的神经化学可塑性中的作用。阿片类药物依赖诱导的渐进性腹腔注射吗啡治疗。吗啡依赖组于末次注射吗啡后6 h取PGi细胞核进行基因表达检测。在自发戒断阶段，大鼠接受与吗啡组相同的慢性治疗。在末次注射吗啡后24、48和72 h提取PGi用于基因表达测定。使用标准化为P-actin基因表达的半定量RT-PCR测定PGi核中BDNF和NT-3的表达。结果表明，吗啡慢性给药可显著增加PGi中BDNF和NT-3基因的表达。自发戒断组BDNF/NT-3基因表达较对照组高。由此看来，源自PGi的BDNF/NT-3信号通路在阿片诱导的LC神经元适应性变化中是必不可少的。(C)2007爱思唯尔有限公司版权所有。
Locus coeruleus (LC) plays a key role in opioid dependence and withdrawal. Chronic morphine administration induces neurochemical adaptations in the noradrenergic system. The nature of signal responsible for opiate-induced adaptations of noradrenergic neurons in LC is not well defined. Neurotrophins-signaling pathways such as brain derived neurotrophic factor (BDNF) and Neurotrophin-3 (NT-3) play a key role for regulating the noradrenergic response of LC neurons to opiates. The nucleus paragiganto-cellularis (PGi) is one of the two major afferents to LC. The present study was designed to evaluate the expression of BDNF and NT-3 in the context of opiate dependence and withdrawal in PGi. Such data are important because they could reveal the role of PGi as an additional source of BDNF and NT-3 in the neurochemical plasticity of LC neurons. Opiate dependence was induced by a progressive intraperitoneal treatment of morphine. In morphine dependent group PGi nucleus was extracted for gene expression assay 6 h after the last injection of morphine. In spontaneous withdrawal, rats received the same chronic treatment as morphine group. PGi was extracted for gene expression assay 24, 48 and 72 h after the last injection of morphine. PGi nucleus was assayed for the expression of BDNF and NT-3 using semi-quantitative RT-PCR normalized to P-actin gene expression. Results showed that chronic administration of morphine significantly increased BDNF and NT-3 gene expression in PGi. In spontaneous withdrawal, BDNF/NT-3 genes expression were high in comparison to control group. It seems that BDNF/NT-3-signaling pathway originating from PGi is essential for opiate-induced adaptations of the LC neurons. (C) 2007 Elsevier Ltd. All rights reserved.