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大脑衍生的神经营养因子在老化的大脑中支持细胞周围细胞和血管平衡
Qinghua Luo1,2, Wenqiang Quan2,3, Qian Cao2,4
1Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Acta neuropathologica communications
|December 2, 2025
概括
大脑衍生神经营养因子 (BDNF) 在衰老中的损失会损害大脑微血管结构. BDNF信号通过Akt激活皮质细胞PDGFRβ的表达,保持老年大脑中的微血管健康.
科学领域:
- 神经科学是一个神经科学.
- 血管生物学 血管生物学
- 衰老研究研究 衰老研究
背景情况:
- 大脑的微血管循环随着年龄的增长而下降,与细胞周围细胞损失有关.
- 在老年大脑中,来自大脑的神经营养因子 (BDNF) 的水平下降.
- BDNF与大脑周细胞/微血管平衡之间的关系尚不清楚.
研究的目的:
- 研究BDNF在调节大脑周细胞和微血管恒温中的作用.
- 阐明BDNF影响皮细胞和微血管的分子机制.
- 确定与年龄有关的脑血管衰退的潜在治疗点.
主要方法:
- 对老年和年轻小鼠的比较分析,包括Bdnf基因淘汰模型.
- 免疫组织化学,西部斑块和流细胞计量以量化微血管和细胞周细胞.
- 单细胞测序和转录组分析以表征细胞群.
- 在体外研究中,使用培养的细胞周细胞接受了BDNF和Akt抑制剂的治疗.
主要成果:
- 降低成熟的BDNF水平与老年大脑中微血管长度,分支和危细胞数量的减少相关.
- 神经元或星球细胞中BDNF缺乏导致大脑微血管和周细胞标记物减少.
- 通过Akt信号激活,BDNF治疗增加了周细胞PDGFRβ的表达.
- 大脑皮细胞的一个子集表达TrkB,BDNF受体.
结论:
- BDNF在维持大脑周细胞和微血管恒温中发挥着至关重要的作用.
- 通过Akt通路激活的BDNF信号,可以提高皮细胞中PDGFRβ的表达.
- 这种BDNF介导的机制对于调节老化大脑中的微血管完整性至关重要.
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