Insulin-like growth factor 2 mitigates depressive behavior in a rat model of chronic stress

Insulin-like growth factor 2 mitigates depressive behavior in a rat model of chronic stress
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胰岛素样生长因子 2 可减轻慢性应激大鼠模型的抑郁行为

DOI:
10.1016/j.neuropharm.2014.10.011
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发表时间:
2015-02-01
期刊:
影响因子:
4.7
通讯作者:
Li, Chang-Qi
Li, Chang-Qi
中科院分区:
医学2区
文献类型:
--
作者:
Luo, Yan-Wei;Xu, Yang;Li, Chang-Qi

文献摘要

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抑郁症是一种常见的与慢性压力有关的精神疾病。胰岛素样生长因子2(IGF 2)是一种生长因子,在发育和成年期间在大脑中发挥重要作用。在这里,IGF 2在海马表达的作用进行了研究,在抑郁症大鼠模型。建立慢性束缚应激(CRS)大鼠抑郁模型,采用蔗糖偏好实验(SPT)、强迫游泳实验(FST)和皮质酮水平测定等方法,观察CRS对大鼠抑郁行为的影响。海马IGF 2水平显着低于CRS大鼠比对照组,因为是pERK 1/2和GluR 1的水平。慢病毒介导的海马IGF 2过表达减轻了束缚大鼠的抑郁行为,提高了pERK 1/2和GluR 1蛋白的水平,但不影响pGSIC 3 β、GluR 2、NMDAR 1和NMDAR 2A的表达。这些结果表明,慢性束缚应激诱导抑郁行为,这可能是通过ERK依赖的IGF 2信号转导介导的,指出该分子途径的抗抑郁作用。(C)2014爱思唯尔有限公司版权所有。
Depression is a common psychiatric disorder associated with chronic stress. Insulin-like growth factor 2 (IGF2) is a growth factor that serves important roles in the brain during development and at adulthood. Here, the role of IGF2 expression in the hippocampus was investigated in a rat model of depression. A chronic restraint stress (CRS) model of depression was established in rats, exhibiting depression-like behavior as assessed with the sucrose preference test (SPT) and forced swimming test (FST), and with evaluation of the corticosterone levels. Hippocampal IGF2 levels were significantly lower in rats suffering CRS than in controls, as were levels of pERK1/2 and GluR1. Lentivirus-mediated hippocampal IGF2 overexpression alleviated depressive behavior in restrained rats, elevated the levels of pERK1/2 and GluR1 proteins, but it did not affect the expression of pGSIC3 beta, GluR2, NMDAR1, and NMDAR2A. These results suggest the chronic restraint stress induces depressive behavior, which may be mediated by ERK-dependent IGF2 signaling, pointing to an antidepressant role for this molecular pathway. (C) 2014 Elsevier Ltd. All rights reserved.