运动训练和BDNF注射改变了粉样蛋白前体蛋白 (APP) 处理酶,并改善了认知能力
Bradley J Baranowski1, Ahmad Mohammad1, Michael S Finch1
1Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada.
Journal of applied physiology (Bethesda, Md. : 1985)
|June 1, 2023
概括
运动和来自大脑的神经营养因子 (BDNF) 通过改变粉样蛋白前体蛋白处理来改善认知功能并降低阿尔茨海默病的风险. BDNF注射模仿了运动的益处,为神经退行提供了潜在的治疗策略.
科学领域:
- 神经科学和神经退行性疾病
- 运动生理学和认知健康
- 分子生物学和生物化学 分子生物学和生物化学
背景情况:
- 众所周知,运动可以减轻认知衰老,神经退行以及阿尔茨海默病 (AD) 风险.
- 已被证明,急性运动会降低β位粉样蛋白前体蛋白分裂酶1 (BACE1) 的活性,BACE1是粉样蛋白β (Aβ) 生产中的关键酶.
- 脑衍生神经营养因子 (BDNF) 是一种运动诱导的神经营养因子,在突触可塑性和神经元存活中起着至关重要的作用,并且已涉及粉样蛋白前体蛋白 (APP) 处理.
研究的目的:
- 调查BDNF治疗是否可以诱导与运动训练相似的APP处理中的生化适应.
- 探索BDNF作为预防或治疗AD等神经退行性疾病的治疗剂的潜力.
主要方法:
- 雄性C57BL6/J小鼠被分为四组:对照组,运动训练组,BDNF注射组,运动和BDNF治疗组合组.
- 一个为期8周的干预期涉及渐进式跑步机训练和/或皮下BDNF注射.
- 用一种新的物体识别测试来评估认知功能,并收集血清,前额叶皮质和海马体组织进行生物化学分析.
主要成果:
- 耐力运动和BDNF治疗都显著改善了小鼠的识别记忆.
- BDNF注射和运动训练导致前额叶皮层中BACE1活性降低,ADAM10活性增加,这表明APP处理发生了有利的转变.
- 通过BDNF治疗观察到的生物化学和认知效益与通过运动训练获得的效益相当.
结论:
- 这项研究表明,慢性外围BDNF管理可以有效调节APP处理酶并增强认知功能,反映运动的影响.
- 这些发现强调了针对BDNF途径的治疗潜力,用于预防和治疗神经退行性疾病,特别是阿尔茨海默病.
- 未来的研究应该专注于开发增加BDNF水平并降低BACE1活性的干预措施,以使风险人群受益.
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