GM1 GANGLIOSIDE CORRECTS RAT BRAIN CHOLINERGIC DEFICITS

GM1 神经节苷脂可纠正大鼠大脑胆碱能缺陷

• 批准号: 2051761
• 负责人: MARIA H NEFF
• 金额: $ 16.13万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2051761
• 关键词: acetylcholine; aging; behavior test; brain disorder chemotherapy; brain metabolism; choline acetyltransferase; cholinergic agents; cognition disorders; corpus striatum; drug interactions; gangliosides; growth factor receptors; hippocampus; in situ hybridization; injection /infusion; laboratory rat; learning; neural degeneration; neuropharmacology; neurotrophic factors; northern blottings; polymerase chain reaction; receptor binding; receptor expression

Aging is associated with a loss of brain neurotransmitter function. The loss of cholinergic neurons apparently parallels the loss of cognitive function. We found that IP administration of GM1 ganglioside, a normal constituent of brain membranes, enhanced acetylcholine (ACh) content in the striatum and choline uptake in the striatum and hippocampus of old (22-24 month old) rats, but had no effect in young rats. GM1 administered by intracerebroventricular (ICV) infusion also increased the aforementioned cholinergic markers as well as increased choline acetyltransferase (ChAT) activity in the striatum of old rats. The improvement of cholinergic neurochemistry was accompanied by improvement of approach/avoidance learning in the old animals. Nerve growth factor (NGF) given ICV induced similar biochemical responses. Co-administration of NGF and GM1 appeared to be more effective than either alone for enhancing ChAT activity in striatum. Since GM1 and NGF induce similar responses on cholinergic neurochemical markers in old animals, we postulate that there may be a common link between them. The goals of this proposal are to: (1) explore the consequences of administering GM1 on cholinergic parameters in the brain of aged rats; (2) investigate the fate of the exogenously administered GM1; (3) to study whether there is an interaction between GM1 and NGF responsive systems. Our findings suggest that GM1 may have significant therapeutic potential for treating the neurochemical deficits and the loss of cognitive ability associated with aging.

衰老与脑神经递质功能的丧失有关。 这 胆碱能神经元的丧失显然与认知的丧失相似 功能。 我们发现IP给药GM1神经节，正常 脑膜的组成，增强的乙酰胆碱（ACH）含量 老纹状体和海马中的纹状体和胆碱吸收 （22-24个月大）大鼠，但对年轻大鼠没有任何作用。 GM1 通过脑室内（ICV）输注给药也增加了 上述胆碱能​​标记和胆碱增加 老鼠纹状体中的乙酰基转移酶（聊天）活性。 这 胆碱能神经化学的改善伴随着改善 旧动物中的方法/回避学习。 神经生长因子 （NGF）给定ICV引起了类似的生化反应。 共同管理 NGF和GM1似乎比单独使用的更有效 增强纹状体中的聊天活动。 由于GM1和NGF诱导类似 对老动物中胆碱能神经化学标记的反应，我们 假设它们之间可能存在共同的联系。 目标 该建议是：（1）探索管理GM1的后果 关于老年大鼠大脑的胆碱能参数； （2）调查 外源给予GM1的命运； （3）研究是否存在 GM1和NGF响应​​系统之间的相互作用。 我们的发现 表明GM1可能具有明显的治疗潜力 神经化学缺陷和相关认知能力的丧失 随着衰老。