Drew Cheney J G, Kyd Rachel J, Morton A Jennifer
Department of Pharmacology, University fo Cambridge, UK.
Hum Mol Genet. 2007 Oct 1;16(19):2288-305. doi: 10.1093/hmg/ddm181. Epub 2007 Jul 24.
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.
复合体蛋白是调节神经递质释放的突触前蛋白。在几种神经退行性疾病和精神疾病中都可见到复合体蛋白1（Cplx1）的异常表达，而这些疾病中社交行为紊乱很常见。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表达的变化是否导致了Cplx1失调的疾病中的精神症状。为了研究这一点，我们检测了复合体蛋白1基因敲除小鼠（Cplx1(-/-)）的认知和社交行为。Cplx1(-/-)小鼠有严重的共济失调，这限制了它们执行协调运动任务的能力。然而，当我们训练幼年Cplx1(-/-)小鼠游泳时，它们在双选游泳实验中没有表现出认知障碍的迹象。相比之下，虽然Cplx1(-/-)小鼠的嗅觉辨别正常，但它们在食物偏好的社会传递任务（另一种认知范式）中失败了。这是由于异常的社交互动，而非认知障碍、焦虑增加或新事物恐惧。当我们直接测试社交行为时，Cplx1(-/-)小鼠没有表现出对社交新奇性的偏好。此外，在定居者-入侵者范式中，雄性Cplx1(-/-)小鼠没有表现出野生型雄性对入侵小鼠典型的攻击行为。我们的研究结果共同表明，除了已经描述的严重运动和探索缺陷外，Cplx1(-/-)小鼠在社交行为方面也有明显缺陷。因此，大脑中复合体蛋白1水平的异常可能导致了该蛋白失调的人类疾病的心理社会方面的问题。
