星形胶质细胞
突触
生物
神经科学
自噬
海马体
树突棘
神经退行性变
突触可塑性
认知功能衰退
平衡
海马结构
细胞生物学
痴呆
疾病
内科学
中枢神经系统
医学
细胞凋亡
生物化学
受体
作者
Eunbeol Lee,Yeon‐Joo Jung,Yu Rim Park,Seongjoon Lim,Youngjin Choi,Se Young Lee,Chan Hyuk Kim,Ji Young Mun,Won‐Suk Chung
出处
期刊:Nature Aging
日期:2022-08-01
卷期号:2 (8): 726-741
被引量:26
标识
DOI:10.1038/s43587-022-00257-1
摘要
The aging brain exhibits a region-specific reduction in synapse number and plasticity. Although astrocytes play central roles in regulating synapses, it is unclear how changes in astrocytes contribute to age-dependent cognitive decline and vulnerability to neurodegenerative diseases. Here, we identified a unique astrocyte subtype that exhibits dysregulated autophagy and morphology in aging hippocampus. In these autophagy-dysregulated astrocytes (APDAs), autophagosomes abnormally accumulate in swollen processes, impairing protein trafficking and secretion. We found that reduced mammalian target of rapamycin (mTOR) and proteasome activities with lysosomal dysfunction generate APDAs in an age-dependent manner. Secretion of synaptogenic molecules and astrocytic synapse elimination were significantly impaired in APDAs, suggesting that APDAs have lost their ability to control synapse number and homeostasis. Indeed, excitatory synapses and dendritic spines associated with APDAs were significantly reduced. Finally, we found that mouse brains with Alzheimer's disease showed a significantly accelerated increase in APDAs, suggesting potential roles for APDAs in age- and Alzheimer's disease-related cognitive decline and synaptic pathology.
科研通智能强力驱动
Strongly Powered by AbleSci AI