Prolonged alcohol intake leads to reversible depression of corticotropin-releasing hormone and vasopressin immunoreactivity and mRNA levels in the parvocellular neurons of the paraventricular nucleus
Prolonged alcohol intake leads to reversible depression of corticotropin-releasing hormone and vasopressin immunoreactivity and mRNA levels in the parvocellular neurons of the paraventricular nucleus
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DOI：
10.1016/s0006-8993(02)03346-2
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发表时间：
2002-11-01
期刊：
影响因子：
2.9
通讯作者：
Madeira, MD
中科院分区：
文献类型：
--
作者：
Silva, SM;Paula-Barbosa, MM;Madeira, MD
酒精激活下丘脑-垂体-肾上腺（HPA）轴的能力在基于急性和短期实验范式的研究中得到了很好的证明。在此，我们已经解决了这样的可能性，即长期暴露于最初有效刺激皮质类固醇分泌的乙醇浓度可能会诱导HPA轴反应的改变，而这种改变不能通过较短的暴露来证明。使用传统的组织学技术，免疫组织化学和原位杂交，我们已经研究了内侧小细胞分裂室旁核（PVNMP），合成和表达促肾上腺皮质激素释放激素（CRH）和加压素（VP）的组成神经元，在大鼠提交6个月的乙醇治疗和退出（2个月后6个月的酒精摄入量）。乙醇处理和撤回没有产生神经元损失的PVNmp。然而，CRH和VP免疫反应神经元的总数和CRH mRNA水平显着减少乙醇处理。在撤回的大鼠，CRH和VP免疫染色的神经元和CRH的基因表达的数量增加相对于乙醇处理的大鼠，并没有不同于对照组。没有显着的变化，检测到VP mRNA水平作为乙醇处理或撤退的结果。这些结果表明，长期酒精摄入钝化CRH和VP在PVN的小细胞神经元的表达，这种影响是，至少部分，可逆的撤退。他们还表明，对乙醇影响的耐受性的发展涉及发生在下丘脑水平的变化。(C)2002 Elsevier Science B. V.保留所有权利。
The ability of alcohol to activate the hypothalamic-pituitary-adrenal (HPA) axis is well documented in investigations based in acute and short-term experimental paradigms. Herein, we have addressed the possibility that the prolonged exposure to ethanol concentrations that are initially effective in stimulating corticosteroid secretion might induce alterations in the response of the HPA axis that cannot be evinced by shorter exposures. Using conventional histological techniques, immunohistochemistry and in situ hybridization, we have examined the medial parvocellular division of the paraventricular nucleus (PVNmp), and the synthesis and expression of corticotropin-releasing hormone (CRH) and vasopressin (VP) by its constituent neurons, in rats submitted to 6 months of ethanol treatment and to withdrawal (2 months after 6 months of alcohol intake). Ethanol treatment and withdrawal did not produce neuronal loss in the PVNmp. However, the total number of CRH- and VP-immunoreactive neurons and the CRH mRNA levels were significantly decreased by ethanol treatment. In withdrawn rats, the number of CRH- and VP-immunostained neurons and the gene expression of CRH were increased relative to ethanol-treated rats and did not differ from those of controls. No significant variations were detected in VP mRNA levels as a result of ethanol treatment or withdrawal. These results show that prolonged alcohol intake blunts the expression of CRH and VP in the parvocellular neurons of the PVN, and that this effect is, partially at least, reversible by withdrawal. They also suggest that the development of tolerance to the effects of ethanol involve changes that take place at the hypothalamic level. (C) 2002 Elsevier Science B.V. All rights reserved.