Complexin 1 knockout mice exhibit marked deficits in social behaviours but appear to be cognitively normal
Complexin 1 knockout mice exhibit marked deficits in social behaviours but appear to be cognitively normal
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DOI：
10.1093/hmg/ddm181
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发表时间：
2007-10-01
影响因子：
3.5
通讯作者：
Morton, A. Jennifer
中科院分区：
文献类型：
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作者：
Drew, Cheney J. G.;Kyd, Rachel J.;Morton, A. Jennifer
复合蛋白是调节神经递质释放的突触前蛋白。复杂蛋白1 （Cplx1）的异常表达见于几种神经退行性疾病和精神疾病，其中社会行为紊乱是常见的。这些疾病包括帕金森病、阿尔茨海默病、精神分裂症、重度抑郁症和双相情感障碍。我们想知道Cplx1表达的变化是否有助于Cplx1失调的疾病的精神成分。为了研究这一点，我们研究了复杂蛋白1敲除小鼠（Cplx1(-/-)）的认知和社会行为。Cplx1（-/-）小鼠有严重的共济失调，限制了它们执行协调运动任务的能力。然而，当我们教幼年Cplx1（-/-）小鼠游泳时，它们在两种选择的游泳池中没有表现出认知障碍的迹象。相比之下，虽然Cplx1（-/-）小鼠的嗅觉辨别是正常的，但Cplx1（-/-）小鼠在另一种认知范式食物偏好任务的社会传递中失败。这是由于不正常的社交互动，而不是认知障碍、焦虑加剧或新恐惧症。当我们直接测试社会行为时，Cplx1（-/-）小鼠未能表现出对社会新颖性的偏好。此外，在常驻-入侵者范式中，雄性Cplx1（-/-）小鼠对入侵小鼠没有表现出典型的野生型雄性的攻击行为。我们的研究结果表明，除了前面描述的严重的运动和探索缺陷外，Cplx1（-/-）小鼠在社交行为方面也有明显的缺陷。因此，大脑中复杂蛋白1水平的异常可能导致这种蛋白质失调的人类疾病的心理-社会方面。
Complexins are presynaptic proteins that modulate neurotransmitter release. Abnormal expression of complexin 1 (Cplx1) is seen in several neurodegenerative and psychiatric disorders in which disturbed social behaviour is commonplace. These include Parkinsons's disease, Alzheimer's disease, schizophrenia, major depressive illness and bipolar disorder. We wondered whether changes in Cplx1 expression contribute to the psychiatric components of the diseases in which Cplx1 is dysregulated. To investigate this, we examined the cognitive and social behaviours of complexin 1 knockout mice (Cplx1(-/-)) mice. Cplx1(-/-) mice have a profound ataxia that limits their ability to perform co-ordinated motor tasks. Nevertheless, when we taught juvenile Cplx1(-/-) mice to swim, they showed no evidence of cognitive impairment in the two-choice swim tank. In contrast, although olfactory discrimination in Cplx1(-/-) mice was normal, Cplx1(-/-) mice failed in the social transmission of food preference task, another cognitive paradigm. This was due to abnormal social interactions rather than cognitive impairments, increased anxiety or neophobia. When we tested social behaviour directly, Cplx1(-/-) mice failed to demonstrate a preference for social novelty. Further, in a resident-intruder paradigm, male Cplx1(-/-) mice failed to show the aggressive behaviour that is typical of wild-type males towards an intruder mouse. Together our results show that in addition to the severe motor and exploratory deficits already described, Cplx1(-/-) mice have pronounced deficits in social behaviours. Abnormalities in complexin 1 levels in the brain may therefore contribute to the psycho-social aspects of human diseases in which this protein is dysregulated.