CHRONIC ETHANOL EXPOSURE AND NEUROPLASTICITY

长期接触乙醇与神经可塑性

基本信息

批准号：
3109372
负责人：
JAMES R WEST
金额：
$ 10.49万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-09-01 至 1987-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3109372
关键词：
acetylcholinesterase afferent nerve alcoholic beverage consumption alcoholism /alcohol abuse autoradiography axon cellular pathology chronic brain damage denervation drug adverse effect ethanol experimental brain lesion hippocampus histochemistry /cytochemistry image processing nervous system regeneration neural plasticity neuroanatomy

项目摘要

It has been postulated that axon sprouting may be a mechanism which underlies some recovery of function following brain damage. Ethanol exposure may have deleterious effects on sprouting and recovery regardless of whether the damage is ethanol-induced or induced by trauma. However, almost no information is available concerning whether CNS neurons exposed chronically to ethanol are even capable of sprouting. The purpose of this proposal is to evaluate the effects of ethanol on sprouting in the adult mammalian brain. For several reasons, monitoring the reorganization of the rat dentate gyrus after partial deafferentation (by the unilateral removal of the entorhinal cortex) will be the method used to assess the effects of ethanol on sprouting: 1) unlike ethanol-induced damage, the entorhinal lesion leaves the contralateral region virtually intact, allowing an intraanimal control which increases the power of quantitative analysis; 2) it will provide data directly related to whether trauma-induced sprouting is retarded or inhibited by ethanol; and 3) it permits focusing on the behavioral recovery of a specific deficit that has been linked previously to sprouting. Quantitative methods including computerized image processing of acetyl-cholinesterase (AChE) histochemical and anterograde autoradiographic pathway tracing techniques will be used to evaluate the stereotypic sprouting responses of the septal, commissural, and crossed temperodentate projections to the dentate gyrus. Recovery of function will be evaluated by monitoring changes in spontaneous alternation correlated with neuroanatomical measures of sprouting within the same animals. By determining if long-term ethanol exposure inhibits sprouting and recovery. it will then be possible to assess whether abstinence has a positive (recoupable) affect on sprouting and recovery. These data will be important for developing and modifying theories to account for the reversibility and recovery from ethanol-induced and lesion-induced brain damage in alcoholics.

有人认为，轴突发芽可能是一种机制脑损伤后功能的恢复是基础。乙醇无论如何，暴露对发芽和恢复都有有害影响损伤是由乙醇引起的还是由创伤引起的。然而，几乎没有关于CNS神经元暴露的信息长期到乙醇甚至能够发芽。这个目的建议是评估乙醇对成人发芽的影响哺乳动物的大脑。由于几个原因，监视重组部分脱落后的大鼠齿状回（通过单侧去除内嗅皮层的）将是用于评估影响的方法发芽中的乙醇：1）与乙醇引起的损害不同病变使对侧区域几乎完好无损，允许人体内控制增加了定量分析的能力； 2）它将提供与创伤引起的发芽直接相关的数据被乙醇延迟或抑制； 3）它允许关注以前已链接的特定赤字的行为恢复发芽。定量方法，包括计算机图像处理乙酰基胆碱酯酶（ACHE）组织化学和顺序放射自显影途径追踪技术将用于评估刻板印象的陈规定型发芽反应对齿状回的温度态度投影。功能的恢复将通过监视自发交替相关的变化来评估在同一动物中发芽的神经解剖学测量。经过确定长期乙醇暴露是否抑制发芽和恢复。然后将有可能评估禁欲是否有积极（可回收）对发芽和恢复的影响。这些数据将是对于开发和修改理论以说明可逆性和从乙醇引起的和病变诱导的大脑中恢复酗酒者的损害。