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γ-干扰素对焦虑样和抑郁样行为作用的进一步证据:海马神经发生和神经生长因子产生的参与。

Further evidence for the role of interferon-gamma on anxiety- and depressive-like behaviors: involvement of hippocampal neurogenesis and NGF production.

作者信息

Campos Alline C, Vaz Gabriela N, Saito Viviane M, Teixeira Antonio L

机构信息

Group of Neuroimmunology, Laboratory of Immunopharmacology, Institute of Biological Sciences and School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil; Infectious Diseases and Tropical Medicine Graduate Program, Medical School, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.

Group of Neuroimmunology, Laboratory of Immunopharmacology, Institute of Biological Sciences and School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil; Infectious Diseases and Tropical Medicine Graduate Program, Medical School, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.

出版信息

Neurosci Lett. 2014 Aug 22;578:100-5. doi: 10.1016/j.neulet.2014.06.039. Epub 2014 Jul 1.

DOI:10.1016/j.neulet.2014.06.039
PMID:24993299
Abstract

A series of evidence suggests that interferon-gamma (IFN-γ) plays an important role in central nervous system (CNS) functions. However, previous studies have obtained inconsistent results regarding the role of IFN-γ in modulating emotion-related behaviors. The present study aimed to evaluate the behavioral profile of IFN-γ knockout (K.O.) mice in models of anxiety and depression. Male C57Bl6 wild type (WT) or IFN-γ K.O. mice were submitted to the following tests: contextual fear conditioning (CFC), elevated plus maze (EPM), open field (OF) and forced swimming test (FST). To explore the possible neurobiological mechanisms involved, we also assessed hippocampal neurogenesis by means of hippocampal doublecortin expression, and the levels of brain-derived neurothophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus and prefrontal cortex. Our results suggested that IFN-γ K.O. mice exhibited an anxiogenic profile in CFC, EPM and OF tests. In FST, the K.O. group spent more time immobile than the WT group. The number of doublecortin positive cells was reduced in the dentate gyrus, and the expression of NGF was down regulated in the prefrontal cortex of IFN-γ K.O. mice. Our results suggest that IFN-γ is involved in CNS plasticity, contributing to the modulation of anxiety and depressive states.

摘要

一系列证据表明,γ-干扰素(IFN-γ)在中枢神经系统(CNS)功能中发挥着重要作用。然而,先前的研究在IFN-γ调节情绪相关行为的作用方面得出了不一致的结果。本研究旨在评估IFN-γ基因敲除(K.O.)小鼠在焦虑和抑郁模型中的行为特征。将雄性C57Bl6野生型(WT)或IFN-γ K.O.小鼠进行以下测试:情境恐惧条件反射(CFC)、高架十字迷宫(EPM)、旷场试验(OF)和强迫游泳试验(FST)。为了探究其中可能涉及的神经生物学机制,我们还通过海马双皮质素表达评估了海马神经发生,并检测了海马和前额叶皮质中脑源性神经营养因子(BDNF)和神经生长因子(NGF)的水平。我们的结果表明,IFN-γ K.O.小鼠在CFC、EPM和OF测试中表现出焦虑样特征。在FST中,K.O.组比WT组静止不动的时间更长。IFN-γ K.O.小鼠齿状回中双皮质素阳性细胞数量减少,前额叶皮质中NGF表达下调。我们的结果表明,IFN-γ参与中枢神经系统可塑性,有助于调节焦虑和抑郁状态。

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