Changes in calcium currents and GABAergic spontaneous activity in cultured rat hippocampal neurons after a neurotropic influenza A virus infection
Changes in calcium currents and GABAergic spontaneous activity in cultured rat hippocampal neurons after a neurotropic influenza A virus infection
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DOI：
10.1016/s0361-9230(01)00536-6
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发表时间：
2001-06-01
影响因子：
3.8
通讯作者：
Kristensson, K
中科院分区：
文献类型：
--
作者：
Brask, J;Owe-Larsson, B;Kristensson, K
为了研究甲型流感病毒（A/WSN/33）嗜神经株可能影响神经元功能或导致神经细胞死亡的机制，用该病毒感染胚胎大鼠的海马培养物。在感染的培养物中，大约70%的神经元对病毒抗原呈免疫阳性，并在全细胞膜片钳记录中显示电压依赖性Ca 2+电流降低，但其他膜特性或胞质Ca 2+浓度没有变化。这些免疫阳性神经元在感染后3-4天发生凋亡。Ca 2+通道抑制剂对神经元存活无显著影响。免疫阴性的神经元群体存活，但与对照组相比，γ-氨基丁酸来源的微型抑制性突触后电流的频率增加。α-氨基-羟基-5-甲基异恶唑-4-丙酸氢溴酸盐（AMPA）受体介导的微小兴奋性突触后电流的频率没有改变。使用Semliki森林病毒系统过表达的病毒核蛋白，定位于树突棘，如辅肌动蛋白的双重免疫标记所示，但本身并不引起神经元死亡或突触传递的变化，如AMPA介导的兴奋性突触后电流所测量。我们的研究结果表明，A型流感病毒感染可引起海马神经元的选择性神经生理学变化，即使在病毒抗原被清除后，这些变化也会持续存在。(C)2001 Elsevier Science Inc.
In order to study mechanisms by which a neurotropic strain of influenza A virus (A/WSN/33) may affect neuronal function or cause nerve cell death, hippocampal cultures from embryonic rats were infected with this virus. Approximately 70% of the neurons in the infected cultures became immunopositive for viral antigens and showed reduced voltage-dependent Ca2+ currents in whole-cell patch clamp recordings, but no changes in other membrane properties or in cytosolic Ca2+ concentration were seen. These immunopositive neurons underwent apoptosis 3-4 days; after infection. Ca2+ channel inhibitors had no significant effect on neuronal survival. The immunonegative population of neurons survived, but displayed increased frequency of miniature inhibitory postsynaptic currents of gamma -amino-butyric acid origin compared with controls. The frequency of alpha -amino-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA) receptor-mediated miniature excitatory postsynaptic currents was not altered. Viral nucleoproteins, overexpressed using the Semliki Forest virus system, were localized to the dendritic spines as shown by double immunolabeling with actinin, but did not by themselves cause neuronal death or changes in synaptic transmission as measured by AMPA-mediated excitatory postsynaptic currents. Our results show that an influenza A virus infection can cause selective neurophysiological changes in hippocampal neurons and that these can persist even after the viral antigens have been cleared. (C) 2001 Elsevier Science Inc.