Glial expression of Borna disease virus phosphoprotein induces behavioral and neurological abnormalities in transgenic mice
Glial expression of Borna disease virus phosphoprotein induces behavioral and neurological abnormalities in transgenic mice
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DOI：
10.1073/pnas.1531155100
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发表时间：
2003-07-22
影响因子：
11.1
通讯作者：
Ikuta, K
中科院分区：
文献类型：
--
作者：
Kamitani, W;Ono, E;Ikuta, K
行为障碍的病因学的一个假设是病毒感染诱导神经元细胞功能障碍，导致广泛的行为异常。然而，病毒感染和与人类精神疾病相关的神经行为障碍之间的直接联系尚未确定。在这里，我们表明，在神经胶质细胞中表达博尔纳病病毒（BDV）的磷蛋白（P）的转基因小鼠出现行为异常，如增强的雄性间的侵略性，多动，和空间参考记忆缺陷。我们证明，转基因大脑表现出显着减少脑源性神经营养因子和5-羟色胺受体的表达，以及突触密度显着下降。这些结果表明，BDV P的神经胶质表达导致类似于那些在BDV感染的动物的行为和神经生物学紊乱。此外，缺乏反应性星形胶质细胞增生和神经元变性的大脑表明，P可以直接诱导胶质细胞功能障碍，也表明转基因小鼠可能表现出类似精神病患者的神经病理学和神经生理学异常。我们的结果为探索病毒感染与神经行为障碍之间的关系提供了新的见解。
One hypothesis for the etiology of behavioral disorders is that infection by a virus induces neuronal cell dysfunctions resulting in a wide range of behavioral abnormalities. However, a direct linkage between viral infections and neurobehavioral disturbances associated with human psychiatric disorders has not been identified. Here, we show that transgenic mice expressing the phosphoprotein (P) of Borna disease virus (BDV) in glial cells develop behavioral abnormalities, such as enhanced intermale aggressiveness, hyperactivity, and spatial reference memory deficit. We demonstrate that the transgenic brains exhibit a significant reduction in brain-derived neurotrophic factor and serotonin receptor expression, as well as a marked decrease in synaptic density. These results demonstrate that glial expression of BDV P leads to behavioral and neurobiological disturbances resembling those in BDV-infected animals. Furthermore, the lack of reactive astrocytosis and neuronal degeneration in the brains indicates that P can directly induce glial cell dysfunction and also suggests that the transgenic mice may exhibit neuropathological and neurophysiological abnormalities resembling those of psychiatric patients. Our results provide a new insight to explore the relationship between viral infections and neurobehavioral disorders.