BIDIRECTIONAL REGULATION OF STRESS RESPONSES BY GALANIN IN MICE: INVOLVEMENT OF GALANIN RECEPTOR SUBTYPE 1
BIDIRECTIONAL REGULATION OF STRESS RESPONSES BY GALANIN IN MICE: INVOLVEMENT OF GALANIN RECEPTOR SUBTYPE 1
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DOI：
10.1016/j.neuroscience.2009.02.063
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发表时间：
2009-06-02
期刊：
影响因子：
3.3
通讯作者：
Bartfai, T.
中科院分区：
文献类型：
--
作者：
Mitsukawa, K.;Lu, X.;Bartfai, T.
神经肽甘丙肽已被证明在精神疾病以及其他生物过程中发挥作用，包括通过与三种G蛋白偶联受体（甘丙肽受体亚型1-3（GaIR 1-3））相互作用来调节疼痛阈值。虽然大多数关于甘丙肽在应激相关疾病中的药理学研究都是在大鼠中进行的，但涉及甘丙肽或其受体亚型的基因工程小鼠的不断发展证实了小鼠药理学研究的重要性。目前对小鼠的研究检查了脑室内（i. c. v.）注射甘丙肽的稳态、内分泌和神经解剖学作用，调节束缚应激后的应激反应。此外，使用GaIR 1敲除（KO）小鼠研究了GaIR 1对这些效应的作用。用无线电遥测装置监测核心体温和自发活动。甘丙肽（i. c. v.）减少自发活动，并施加约束应力引起的体温过高的双向影响;高剂量的甘丙肽显着衰减的应力引起的体温过高的反应，而低剂量的甘丙肽适度增强这种反应。甘丙肽的双向作用与应激激素水平（促肾上腺皮质激素和皮质酮）的变化相关。为了从神经解剖学上定位甘丙肽对应激反应的影响，分别在甘丙肽受体丰富的区域、下丘脑的室旁核（PVN）和蓝斑（LC）中评估cFos免疫反应性。高剂量甘丙肽显著诱导LC中的cFos活性，但不诱导PVN中的cFos活性。在GaIR 1 KO小鼠中，高剂量的甘丙肽未能诱导任何上述效应，表明GaIR 1在此处研究的甘丙肽i. c. v.注射引起的运动活性降低和应激抵抗效应中起关键作用。(C)2009年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The neuropeptide galanin has been shown to play a role in psychiatric disorders as well as in other biological processes including regulation of pain threshold through interactions with three G-protein coupled receptors, galanin receptor subtypes 1-3 (GaIR 1-3). While most of the pharmacological studies on galanin in stress-related disorders have been done with rats, the continuous development of genetically engineered mice involving galanin or its receptor subtype(s) validates the importance of mouse pharmacological studies. The present study on mice examined the homeostatic, endocrinological and neuroanatomical effects of the galanin, injected intracerebroventricularly (i.c.v.), in regulation of stress responses after restraint stress. Furthermore, the roles of GaIR1 on these effects were studied using GaIR1 knockout (KO) mice. The core body temperature and the locomotor activity were monitored with radio telemetry devices. Galanin (i.c.v.) decreased locomotor activity and exerted a bidirectional effect on the restraint stress-induced hyperthermia; a high dose of galanin significantly attenuated the stress-induced hyperthermic response, while a low dose of galanin moderately enhanced this response. The bidirectional effect of galanin was correlated with changes in stress hormone levels (adrenocorticotropic hormone and corticosterone). To neuroanatomically localize the effects of galanin on stress response, cFos immunoreactivity was assessed in galanin receptor rich areas; paraventricular nucleus (PVN) of the hypothalamus and the locus coeruleus (LC), respectively. A high dose of galanin significantly induced cFos activity in the LC but not in the PVN. In GaIR1KO mice, a high dose of galanin failed to induce any of the above effects, suggesting the pivotal role of GaIR1 in decreased locomotor activity and stress-resistant effects caused by galanin i.c.v. injection studied here. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.