Park Hoyong, Yu Ji Eun, Kim Sungmin, Nahm Sang-Soep, Chung ChiHye
Department of Biological Sciences, College of Bioscience and Biotechnology, Konkuk University, Seoul, 143-701, South Korea.
Laboratory of Veterinary Anatomy, College of Veterinary Medicine, Konkuk University, Seoul, 143-701, South Korea.
Sci Rep. 2015 Aug 27;5:13440. doi: 10.1038/srep13440.
Influenza virus infection is one of common infectious diseases occurring worldwide. The human influenza virus can infect the central nervous system and cause brain dysfunctions affecting cognition and spatial memory. It has been previously shown that infection with the influenza viral protein within the hippocampus decreases Ca(2+) influx and reduces excitatory postsynaptic currents. However, the neuronal properties of animals surviving neonatal infection have not been investigated. Using a mouse model of neonatal influenza infection, we performed thorough electrophysiological analyses of hippocampal neurotransmission. We found that animals surviving the infection exhibited reduced spontaneous transmission with no significant defects in evoked neurotransmission. Interestingly, the hippocampus of the infected group conducted synaptic transmission with less fidelity upon repeated stimulations and failed to generate action potentials faithfully upon step current injections primarily due to reduced Na(+) influx. The reversal potential for the Na(+) current was hyperpolarized and the activation of Na(+) channels was slower in the infected group while the inactivation process was minimally disturbed. Taken together, our observations suggest that neonatally infected offsprings exhibit noticeable deficits at rest and severe failures when higher activity is required. This study provides insight into understanding the cellular mechanisms of influenza infection-associated functional changes in the brain.
流感病毒感染是全球常见的传染病之一。人类流感病毒可感染中枢神经系统并导致影响认知和空间记忆的脑功能障碍。先前研究表明，海马体内的流感病毒蛋白感染会减少Ca(2+)内流并降低兴奋性突触后电流。然而，新生期感染存活动物的神经元特性尚未得到研究。我们使用新生期流感感染小鼠模型，对海马神经传递进行了全面的电生理分析。我们发现，感染后存活的动物自发传递减少，而诱发神经传递无明显缺陷。有趣的是，感染组海马在重复刺激时突触传递的保真度较低，在阶跃电流注入时无法忠实地产生动作电位，主要原因是Na(+)内流减少。感染组Na(+)电流的反转电位超极化，Na(+)通道的激活较慢，而失活过程受到的干扰最小。综上所述，我们的观察结果表明，新生期感染的后代在静息时表现出明显的缺陷，在需要更高活动时则出现严重故障。本研究为理解流感感染相关脑功能变化的细胞机制提供了见解。
