Neuronal activity and stress differentially regulate hippocampal and hypothalamic corticotropin-releasing hormone expression in the immature rat

Neuronal activity and stress differentially regulate hippocampal and hypothalamic corticotropin-releasing hormone expression in the immature rat
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DOI:
10.1016/s0306-4522(00)00386-9
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发表时间:
2000-01-01
期刊:
影响因子:
3.3
通讯作者:
Baram, TZ
Baram, TZ
中科院分区:
医学3区
文献类型:
--
作者:
Hatalski, CG;Brunson, KL;Baram, TZ

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促肾上腺皮质激素释放激素是神经内分泌应激反应的主要神经调节剂,在未成熟海马中表达,增强主要细胞的谷氨酸受体介导的兴奋。由于多肽影响海马突触效能,其从多肽能神经元间末端的分泌可能增强海马介导的功能,如学习和记忆。然而,尽管有关促肾上腺皮质激素释放激素在中枢神经系统中与应激神经内分泌反应有关的丰度调节的信息已经出现,但海马中调节肽水平的机制尚未确定。在这里,我们测试了一个假设,即在未成熟的大鼠海马中,神经元刺激而不是神经内分泌刺激会影响肽的表达。在低温(激活未成熟大鼠下丘脑垂体-肾上腺系统的生理挑战)和高温激活海马神经元后,测定海马CA1、CA3和齿状回以及下丘脑室旁核中促肾上腺皮质激素释放激素的信使RNA水平。这些研究表明,虽然低温刺激增强了下丘脑中促肾上腺皮质激素释放激素信使RNA的水平,但海马中该神经肽的表达不变。其次,高温刺激海马即刻早期基因和促肾上腺皮质激素释放激素的表达。最后,海马促肾上腺皮质激素释放激素诱导的机制需要神经元刺激,巴比妥酸盐可以消除这一机制。综上所述,这些结果表明,神经元刺激可能调节未成熟大鼠海马促肾上腺皮质激素释放激素的表达,而下丘脑的肽表达受神经内分泌挑战的影响。(c) 2000 ibro。Elsevier Science Ltd.出版。版权所有。
Corticotropin-releasing hormone, a major neuromodulator of the neuroendocrine stress response, is expressed in the immature hippocampus, where it enhances glutamate receptor-mediated excitation of principal cells. Since the peptide influences hippocampal synaptic efficacy, its secretion from peptidergic interneuronal terminals may augment hippocampal-mediated functions such as learning and memory. However, whereas information regarding the regulation of corticotropin-releasing hormone's abundance in CNS regions involved with the neuroendocrine responses to stress has been forthcoming, the mechanisms regulating the peptide's levels in the hippocampus have not yet been determined. Here we tested the hypothesis that, in the immature rat hippocampus, neuronal stimulation, rather than neuroendocrine challenge, influences the peptide's expression. Messenger RNA levels of corticotropin-releasing hormone in hippocampal CA1, CA3 and the dentate gyrus, as well as in the hypothalamic paraventricular nucleus, were determined after cold, a physiological challenge that activates the hypothalamic pituitary adrenal system in immature rats, and after activation of hippocampal neurons by hyperthermia. These studies demonstrated that, while cold challenge enhanced corticotropin-releasing hormone messenger RNA levels in the hypothalamus, hippocampal expression of this neuropeptide was unchanged. Secondly, hyperthermia stimulated expression of hippocampal immediate-early genes, as well as of corticotropin-releasing hormone. Finally, the mechanism of hippocampal corticotropin-releasing hormone induction required neuronal stimulation and was abolished by barbiturate administration.Taken together, these results indicate that neuronal stimulation may regulate hippocampal corticotropin-releasing hormone expression in the immature rat, whereas the peptide's expression in the hypothalamus is influenced by neuroendocrine challenges. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.