VIRAL-INDUCED DYSFUNCTION OF SENSORY NEURONS

病毒引起的感觉神经元功能障碍

• 批准号: 3428293
• 负责人: RICHARD J ZIEGLER
• 金额: $ 2.12万
• 依托单位: UNIVERSITY OF MINNESOTA DULUTH
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1986-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3428293
• 关键词: electrolyte balance; electrophysiology; membrane potentials; mental disorders; mumps virus; neural conduction; neural information processing; neurons; poliovirus; tissue /cell culture

Normal behavior depends upon the proper functioning of the nervous system. Intact neural circuits possessing correct intracellular and intercellular neuronal communications are largely responsible for this functioning. Alteration or disruption of this communication can lead to mental disease. These alterations may be the result of genetic defects, trauma, toxic substances, or infectious agents which either destroy groups or populations of neurons or cause improper communication within or between neurons. Viruses are well known for their ability to infect neurons and kill them during the process of viral replication. Poliovirus infections are a classic example. This loss of neurons results in neural dysfunction with concomitant disease. The ability of viruses to cause neural dysfunction by altering neuronal function is not well documented. This proposal is designed to determine whether noncytolytic virus infections of neurons can cause neuronal dysfunction and thereby play a role in mental disease. Specifically, we are requesting funds for a pilot study to determine if representative neurotrophic viruses, 1) measles virus, 2) mumps virus, 3) a neurotrophic retrovirus can alter specific aspects of neuronal function, i.e. ligand and voltage-gated ionic channels and neuropeptide metabolism. The functional properties that will be examined include generation of action potentials, neurochemical receptor-mediated membrane excitation, neurochemical modulation of ionic channels and neuropeptide content and release. All of these parameters are important for normal functioning of the brain and therefore good mental health. These studies will be performed in vitro with rat or mouse sensory neurons as our "model" neurons. The proposal is not designed to prove a specific noncytolytic virus is involved in a specific mental health problem but to demonstrate they have this potential. Future proposals may address this question.

正常的行为取决于神经系统的正常运作。 完整的神经回路具有正确的细胞内和细胞间 神经元的通讯主要负责这种功能。 这种交流的改变或中断可能导致精神疾病。 这些改变可能是由于遗传缺陷，创伤，毒性 物质或传染性病原体， 或引起神经元内或神经元之间的不适当通信。 众所周知，病毒具有感染神经元并杀死它们的能力 在病毒复制的过程中。 脊髓灰质炎病毒感染是一种 典型的例子 这种神经元的损失导致神经功能障碍， 伴随疾病。 病毒通过以下方式引起神经功能障碍的能力 改变神经元的功能还没有很好的记录。 这项建议是 旨在确定神经元的非溶细胞病毒感染是否可以 导致神经元功能障碍，从而在精神疾病中发挥作用。 具体而言，我们正在申请资金进行试点研究，以确定 代表性的神经营养病毒，1）麻疹病毒，2）腮腺炎病毒，3）a 神经营养性逆转录病毒可以改变神经元功能的特定方面， 即配体和电压门控离子通道和神经肽代谢。 将检查的功能属性包括生成 动作电位，神经化学受体介导的膜兴奋， 离子通道和神经肽含量的神经化学调节， release. 所有这些参数对于正常的功能都很重要。 大脑和良好的心理健康。 这些研究将在体外用大鼠或小鼠感觉神经元进行 作为我们的“模型”神经元。 该提案的目的不是为了证明一个特定的 非细胞溶解性病毒与特定的精神健康问题有关， 证明他们有这个潜力。 未来的提案可能会解决这一问题 问题

项目成果

Mumps virus-induced alterations in cellular excitability during persistent infections.

腮腺炎病毒在持续感染过程中引起细胞兴奋性的改变。

• DOI: 10.1099/0022-1317-68-9-2501
• 发表时间: 1987
• 期刊: The Journal of general virology
• 作者: Ziegler,RJ;Stauffer,EK
• 通讯作者: Stauffer,EK