Moderate doses of alcohol and the developing cerebellum

中等剂量的酒精和发育中的小脑

• 批准号: 6906463
• 负责人: JOHN T GREEN
• 金额: $ 7.58万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6906463
• 关键词: alcoholic beverage consumption; blood tests; brain electrical activity; cerebellar Purkinje cell; cerebellum; cognition disorders; developmental disease /disorder; developmental neurobiology; drug administration rate /duration; early experience; electromyography; embryo /fetus toxicology; fetal alcohol syndrome; laboratory rat; neural degeneration; neural transmission; neurophysiology; neuropsychology; neurotoxicology; reflex

DESCRIPTION (provided by applicant): The long-term objective of this research is to determine the patterns of alcohol consumption during pregnancy that results in long-term damage to the cerebellum. While it is well established that doses of alcohol that produce high blood alcohol concentrations ("binge-like exposure") over a limited portion (postnatal days 4-9) of the human third trimester-equivalent in rats can permanently damage the cerebellum, much less is known about the effects of producing lower blood alcohol concentrations over a more extended period of development. The impact on the cerebellum can be studied by combining eye blink classical conditioning, a cerebellar-dependent task that engages a well-studied and fully delineated cerebellar circuit, with counting of cerebellar cells and recording of neuronal activity in defined areas of the cerebellum. The specific aims of the proposed research are to combine these behavioral, neuroanatomical, and neurophysiological techniques to examine the impact on the adult cerebellum of acute, low dose exposure to alcohol during a longer period of the third trimester than is usually examined. Two experiments are proposed. In Experiment 1, rats will be exposed to a low dose of alcohol once per day across postnatal days 2-11. As adults they will be tested on eyeblink conditioning and cell counts of two cerebellar cell populations critical for learning, interpositus nucleus cells and Purkinje cells, will be made and compared to behavioral performance. In Experiment 2, the same neonatal treatments will be performed and, as adults, rats will be tested on eyeblink conditioning while neuronal activity from the interpositus nucleus is recorded. When completed, these results will provide important evidence regarding the extent to which moderate consumption of alcohol across an extended period of the third trimester impacts the developing cerebellum and will help to determine which alcohol consumption patterns over what time period of development damage the cerebellum. This knowledge is important for developing effective interventions and therapies for children exposed to alcohol prenatally.

描述（由申请人提供）：这项研究的长期目标是确定怀孕期间饮酒的模式，从而导致小脑长期损害。虽然可以很好地确定，在有限的部分（产后4-9天）中，人类三个月等同于大鼠的酒精浓度（“暴饮暴食）暴露”（“暴饮暴食）暴露”可能会永久损害小脑，但对产生较低血液浓度的较高的发育期的较低的血液浓度的影响更少。可以通过将眼睛眨眼经典条件（这是一项小脑依赖性任务结合在一起）来研究小脑的影响，该任务与小脑细胞相关的小脑细胞和小脑细胞的记录以及在Cerebellum定义区域中的神经元活性的记录。拟议的研究的具体目的是将这些行为，神经解剖学和神经生理学技术结合在一起 检查对急性，低剂量暴露于第三个孕期的急性小脑对急性，低剂量暴露于酒精的影响。提出了两个实验。在实验1中，大鼠将在产后2-11天每天暴露于每天一次低剂量的酒精。作为成年人，他们将在8link链接条件和两个小脑细胞群体的细胞计数上进行测试，这对于学习至关重要，将核核细胞和浦肯野细胞与行为性能进行比较。在实验2中，将进行相同的新生儿治疗，并且作为成年人，将在骨blink条件下测试大鼠，同时记录核核的神经元活性。完成后，这些结果将提供重要的证据，表明在三个月的长期内，在多大程度上饮酒会影响发育中的小脑，并有助于确定在哪些时间段的发育时间损害小脑的时间内的饮酒方式。这些知识对于为暴露于饮酒的儿童开发有效的干预措施和疗法很重要。