BDNF FUNCTION IN A NEUROLOGICAL MUTANT MOUSE

神经突变小鼠的 BDNF 功能

• 批准号: 2262020
• 负责人: XIAOXI QIAO
• 金额: $ 2.86万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-12-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2262020
• 关键词: BDNF; FUNCTION; NEUROLOGICAL; MUTANT; MOUSE

This proposal aims at studying the role of BDNF in cerebellar development. It examines the hypothesis that lack of BDNF might result in a epileptic and/or ataxic phenotype. The study takes advantage of a recently described genetic model with selective defect of BDNF in the cerebellum, the recessive single locus mutation stargazer (stg).The most striking features of this neurologic mutation are ataxia, episodic neck retroflexion, and severe generalized spike-wave seizures. It is proposed to characterize mRNA and protein levels of selected neurotrophins and neurotrophin receptors in the cerebellum of stargazer. Further, using intracerebral infusion of BDNF in developing stargazer mice, it will be attempted to reverse or attenuate the observed functional deficits and the cerebellar atrophy observed in the mutant mice. If confirmed to be virtually free of BDNF protein, the stargazer cerebellum will be used to study the effects of chronic treatment with BDNF on the responsiveness of the BDNF receptor. The proposed experiments may ultimately lead to new insights into the roles of neurotrophic factors during brain development and, possibly, into causes and consequences of epileptic seizure activity in the brain. They might also provide information relevant to trophic actor treatment in neurological diseases.

本提案旨在研究 BDNF 在小脑中的作用 发展。它检验了 BDNF 缺乏可能导致的假设 处于癫痫和/或共济失调表型。该研究利用了 最近描述了 BDNF 选择性缺陷的遗传模型 小脑，隐性单基因座突变观星者（stg）。 这种神经系统突变的显着特征是共济失调、阵发性颈部 后屈和严重的全身棘波癫痫发作。建议 表征所选神经营养素的 mRNA 和蛋白质水平， 观星者小脑中的神经营养素受体。此外，使用 在发育中的观星小鼠脑内注射 BDNF，将会 试图扭转或减轻观察到的功能缺陷，并且 在突变小鼠中观察到的小脑萎缩。如果确认是 观星者小脑几乎不含 BDNF 蛋白，将用于 研究 BDNF 长期治疗对反应性的影响 BDNF 受体。拟议的实验可能最终会产生新的结果 深入了解神经营养因子在大脑发育过程中的作用 并可能了解癫痫发作活动的原因和后果 在大脑中。他们还可能提供与营养相关的信息 演员治疗神经系统疾病。