BORNA VIRUS ALTERS PERINATAL BEHAVIOR DEVELOPMENT

博尔纳病毒改变围产期行为发育

• 批准号: 3388458
• 负责人: KATHRYN M. CARBONE
• 金额: $ 11.22万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3388458
• 关键词: antiidiotype antibody; association learning; astrocytes; avoidance behavior; behavior; behavior test; central nervous system; developmental neurobiology; disease /disorder model; eating; encephalitis; encephalitis virus; flow cytometry; hippocampus; immunocytochemistry; in situ hybridization; laboratory rat; limbic system; molecular site; neuroanatomy; neurons; neurotransmitters; newborn animals; parent offspring interaction; pathologic process; perinatal; sensorimotor system; taste threshold; videotape /videodisc; virus replication; water drinking behavior

Viral infections of the human fetus and newborn produce pathological behavior in the neonatal period and beyond. Childhood psychiatric illnesses such as autism may follow perinatal viral infections in the CNS. in this application a multidisciplinary group of virologists, behavioral scientists and neuroanatomists propose to study a model of encephalitis virus infection in the neonate, Borna disease virus (BDV). BDV is a neurotropic virus which persistently infects limbic system neurons and produces behavioral and anatomical abnormalities in the neonatal rat (persistent infection/newborn or PI/NB). Unlike most encephalitis viruses perinatal infection with BDV produces no inflammation in the CNS. PI/NB rats appear grossly normal but have increased motor activity, retarded learning abilities and diminished pain avoidance learning. We propose to study the pathogenesis of behavioral developmental abnormalities produced by perinatal infection with a persistent virus. Specific Aims: 1. In the PI/NB rat which neuroanatomical regions contain neurons infected with BDV? Hypothesis: BDV infects selective neuronal groups in neonatal rats. BDV infected neurons will be identified by immunohistochemical stains for BDV proteins and in situ hybridization for BDV nucleic acids. BDV spreads in cell processes throughout the nervous system; we will chart the dissemination of virus as neural pathways develop. 2. Are characteristic abnormalities in behavior associated with BDV infection of specific neurons in the PI/NB rat? Hypothesis: BDV infection of specific neuron groups in the neonatal rat disrupts normal neurological functions, resulting in characteristic abnormalities in behavior. Using the results from Aim 1, behavior abnormalities related to the dysfunction of the infected neurons will be identified including: social interactions of mother and pup, taste reactivity, learned taste aversion and locomotor activity. Behavioral analyses will be performed on rats inoculated with BDV at sequential timepoints shortly after birth to assess the effects of perinatal infection on the development of these behaviors. 3. Are neurotransmitter distribution and levels affected by neonatal infection with BDV? Hypothesis: Neurochemical development is disturbed by neonatal infection with BDV. Alterations in anatomical distribution and qualitative levels of various neurotransmitters will be characterized immunohistochemically. If regional or global abnormalities are noted, pertinent neurotransmitter levels will be quantitated. 4. What neural cell feature confers specificity for infection with BDV? Hypothesis: BDV binds to a phylogenetically conserved neural cell molecule for entry into the cell, explaining the virus tropism for the nervous system in a wide variety of virus structure will be used to identify and characterize binding sites on susceptible neurons.

人类胎儿和新生儿的病毒感染会产生病理 新生儿期及以后的行为。 童年精神病学 自闭症等疾病可能发生在中枢神经系统围产期病毒感染之后。 在这个应用程序中，一个由病毒学家、行为学家组成的多学科小组 科学家和神经解剖学家提议研究脑炎模型 新生儿病毒感染，博尔纳病病毒（BDV）。 BDV 是一个 持续感染边缘系统神经元的嗜神经病毒 导致新生大鼠行为和解剖异常 （持续感染/新生儿或 PI/NB）。 与大多数脑炎病毒不同 BDV 围产期感染不会引起中枢神经系统炎症。 PI/NB 大鼠看起来非常正常，但运动活动增加，发育迟缓 学习能力和避免痛苦的学习能力减弱。 我们建议 研究行为发育异常的发病机制 由持续性病毒的围产期感染引起。 具体目标： 1. 在 PI/NB 大鼠哪些神经解剖区域含有感染 BDV 的神经元？ 假设：BDV 选择性感染新生大鼠的神经元群。 BDV 通过 BDV 免疫组织化学染色来识别受感染的神经元 蛋白质和 BDV 核酸原位杂交。 BDV 传播于 整个神经系统的细胞过程；我们将绘制图表 随着神经通路的发展，病毒传播。 2.有特色 与特定神经元 BDV 感染相关的行为异常 在 PI/NB 大鼠中？ 假设：BDV 感染特定神经元群 新生大鼠破坏正常的神经功能，导致 行为特征异常。 使用目标 1 的结果， 与受感染神经元功能障碍相关的行为异常 将被识别包括：母亲和小狗的社交互动、味道 反应性、习得性味觉厌恶和运动活动。 行为方面 将在连续接种 BDV 的大鼠上进行分析 出生后不久的时间点评估围产期感染的影响 关于这些行为的发展。 3. 是神经递质 新生儿感染 BDV 的分布和水平有何影响？ 假设：神经化学发育受到新生儿感染的干扰 与 BDV。 解剖分布和质量水平的改变 各种神经递质将通过免疫组织化学进行表征。 如果 注意到区域或整体异常，相关神经递质 水平将被量化。 4. 哪些神经细胞特征赋予特异性 感染 BDV？ 假设：BDV 与系统发育上的 用于进入细胞的保守神经细胞分子，解释了 病毒对神经系统有多种趋向性 病毒结构将用于识别和表征结合位点 易感神经元。