Cytomegalovirus infection inhibits the expression of N-methyl-D-aspartate receptors in the developing mouse hippocampus and primary neuronal cultures
Cytomegalovirus infection inhibits the expression of N-methyl-D-aspartate receptors in the developing mouse hippocampus and primary neuronal cultures
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DOI：
10.1007/s00401-005-0987-7
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发表时间：
2005-05-01
影响因子：
12.7
通讯作者：
Tsutsui, Y
中科院分区：
文献类型：
--
作者：
Kosugi, I;Kawasaki, H;Tsutsui, Y
巨细胞病毒（CMV）是人类发育性脑疾病的最重要的感染性原因。感染偶尔持续存在，并导致神经系统疾病。谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型对突触的发育和可塑性至关重要，但也参与病毒感染期间的神经元兴奋性毒性。本文研究了小鼠巨细胞病毒（MCMV）感染对新生小鼠海马神经元和原代培养神经元NMDA受体表达的影响。病毒抗原主要分布于海马CA 1 ~ CA 3区锥体神经元。免疫组织化学图像分析显示，MCMV感染组海马CA 1区神经元NMDA受体亚单位1（NMDA-R1）蛋白表达量较对照组减少40%。MCMV感染组海马CA 1区神经元NMDA-R1 mRNA原位杂交信号也明显减弱。在原代神经元培养中，MCMV感染的神经元中NMDA-R1表达的减少也通过免疫细胞化学和Western印迹检测到。这些结果表明，MCMV感染的NMDA受体表达的减少可能会导致神经元兴奋性毒性细胞死亡的易感性降低，并可能与MCMV感染的神经元中的病毒持久性和功能障碍的建立有关。
Cytomegalovirus (CMV) is the most significant infectious cause of developmental brain disorders in humans. The infection occasionally persists and causes neurological disorders. The N-methyl-D-aspartate (NMDA) subtype of glutamate receptors is essential for the development and plasticity of synapses, but also is involved in neuronal excitotoxicity during viral infection. Here we investigated the effects of murine CMV (MCMV) infection on the expression of NMDA receptors in the hippocampal neurons of neonatal mice and primary neuronal cultures. Viral antigen was mostly found in hippocampal pyramidal neurons from the CA1 to CA3. Image analysis of immunohistochemistry demonstrated that the expression of NMDA receptor subunit 1 (NMDA-R1) protein in CA1 neurons of MCMV-infected brain was reduced to 40% of that in uninfected brain. The signal of in situ hybridization for NMDA-R1 mRNA was also decreased in CA1 neurons of MCMV-infected brain. In primary neuronal cultures, reduction of NMDA-R1 expression in MCMV-infected neurons was also detected by immunocytochemistry and Western blotting. These results suggest that reduction of NMDA receptor expression by MCMV infection may cause a decrease in the susceptibility of the neurons to excitotoxic cell death, and may be related to the establishment of viral persistence and functional disturbances in MCMV-infected neurons.