Elevated reactive aggression in forebrain-specific Ccn2 knockout mice

IF 3.6 3区 生物学 Q3 CELL BIOLOGY
Ho-Ching Chang, Chi-Hou Ng, Yu-Fu Chen, Yu-Chun Wang, I-Shing Yu, Lukas Jyuhn-Hsiarn Lee, Li-Jen Lee, Kuang-Yung Lee
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Abstract

Cellular communication network factor 2 (CCN2) is a matricellular protein that plays important roles in connective tissue. CCN2 is also expressed in the nervous system; however, its role is still unclear. To explore CCN2 function in the brain, we generated forebrain-specific Ccn2 knockout (FbCcn2 KO) mice. In this study, we examined the behavioral phenotypes of FbCcn2KO mice. Male mice lacking CCN2 in the forebrain exhibited normal locomotion, sensorimotor gating, and social behaviors but signs of anxiety and elevated reactive aggression. We checked the c-fos expression in aggression-related brain regions following the resident-intruder task (RIT), an aggression test. RIT-induced c-fos levels in the medial amygdala (MeA) were higher in FbCcn2−/− mice as compared to controls. However, in the prefrontal cortex, RIT-induced c-fos levels in FbCcn2−/− mice were lower than controls. Our results suggested in male mice lacking CCN2 in the olfaction-related regions, olfactory social cues elicit greater signals in the MeA, resulting in greater reactive aggression in the RIT. Further, lacking CCN2 in the prefrontal cortex, the major area related to inhibitory control and emotion regulation, may lead to signs of anxiety and the failure to suppress aggressive behaviors. Our model is useful in elaborating the mechanism underlying reactive aggression and therapeutic strategies.

Abstract Image

前脑特异性 Ccn2 基因敲除小鼠的反应性攻击性增强
细胞通讯网络因子 2(CCN2)是一种母细胞蛋白,在结缔组织中发挥着重要作用。CCN2 在神经系统中也有表达,但其作用尚不清楚。为了探索CCN2在大脑中的功能,我们培育了前脑特异性Ccn2基因敲除(FbCcn2 KO)小鼠。在这项研究中,我们考察了FbCcn2KO小鼠的行为表型。前脑缺乏CCN2的雄性小鼠表现出正常的运动、感觉运动门控和社交行为,但有焦虑和反应性攻击行为升高的迹象。我们检测了攻击性测试--入侵者任务(RIT)后攻击性相关脑区的c-fos表达。与对照组相比,FbCcn2-/-小鼠内侧杏仁核(MeA)中RIT诱导的c-fos水平更高。然而,在前额叶皮层,RIT诱导的c-fos水平在FbCcn2-/-小鼠中低于对照组。我们的研究结果表明,在嗅觉相关区域缺乏CCN2的雄性小鼠中,嗅觉社交线索会在MeA中引起更大的信号,从而导致在RIT中产生更大的反应性攻击。此外,前额叶皮质是与抑制控制和情绪调节有关的主要区域,如果前额叶皮质中缺乏CCN2,可能会导致焦虑症状和无法抑制攻击行为。我们的模型有助于阐明反应性攻击行为的内在机制和治疗策略。
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来源期刊
CiteScore
6.40
自引率
4.90%
发文量
40
期刊介绍: The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies. Research manuscripts can be published under two different sections : In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research. In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.
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