Ferguson Gregory D, Herschman Harvey R, Storm Daniel R
Department of Pharmacology, Health Sciences Building, University of Washington, Seattle, WA, Box 357280, 98195-7280, USA.
Neuropharmacology. 2004 Sep;47(4):604-11. doi: 10.1016/j.neuropharm.2004.05.008.
Synaptotagmin IV (Syt IV) is a secretory vesicle protein that is broadly expressed in brain and may function as a presynaptic regulator of synaptic release. Because Syt IV and abnormalities in neurotransmission have been implicated in psychiatric disease, we examined Syt IV (-/-) mice in animal models of mood-related behavior. We report that Syt IV (-/-) mice display lower levels of anxiety-like behavior in the elevated plus maze and enhanced locomotion in the open field. Syt IV (-/-) mice also exhibit reduced depression-like behavior and are highly sensitive to the effects of the anti-depressant imipramine in a modified Porsolt forced swim test. However, the physical restraint-induced stress hormone response is normal in Syt IV (-/-) mice. As judged by immunohistochemical criteria, the synaptic structure and connectivity of the hippocampus and raphe nucleus in Syt IV (-/-) mice are indistinguishable from wild-type littermates. These results indicate that Syt IV plays a role in rodent mood-related behavior and suggests Syt IV regulates synaptic function in the neuronal networks that modulate these behaviors.
突触结合蛋白IV（Syt IV）是一种分泌囊泡蛋白，在大脑中广泛表达，可能作为突触释放的突触前调节因子发挥作用。由于Syt IV与神经传递异常已被认为与精神疾病有关，我们在情绪相关行为的动物模型中研究了Syt IV基因敲除（-/-）小鼠。我们报告称，Syt IV（-/-）小鼠在高架十字迷宫中表现出较低水平的焦虑样行为，在旷场实验中运动增强。Syt IV（-/-）小鼠还表现出抑郁样行为减少，并且在改良的波索尔特强迫游泳试验中对抗抑郁药丙咪嗪的作用高度敏感。然而，Syt IV（-/-）小鼠中物理束缚诱导的应激激素反应是正常的。根据免疫组织化学标准判断，Syt IV（-/-）小鼠海马体和中缝核的突触结构和连接性与野生型同窝小鼠没有区别。这些结果表明，Syt IV在啮齿动物情绪相关行为中起作用，并表明Syt IV调节调节这些行为的神经网络中的突触功能。
