神经炎症
肥大细胞
小胶质细胞
免疫系统
神经病理学
神经科学
免疫学
生物
炎症
神经退行性变
疾病
医学
病理
作者
Chih-Chung Jerry Lin,Fanny Herisson,Hoang Lan Le,Nik Ruzyanei Nik Jaafar,Kashish Chetal,Mary K. Oram,K.A. Flynn,Evan P Gavrilles,Ruslan I. Sadreyev,Felipe L. Schiffino,Rudolph E. Tanzi
出处
期刊:Cell Reports
[Elsevier]
日期:2023-09-01
卷期号:42 (9): 113141-113141
标识
DOI:10.1016/j.celrep.2023.113141
摘要
Emerging evidence suggests that peripheral immune cells contribute to Alzheimer’s disease (AD) neuropathogenesis. Among these, mast cells are known for their functions in allergic reactions and neuroinflammation; however, little is known about their role in AD. Here, we crossed 5XFAD mice with mast cell-deficient strains and observed the effects on AD-related neuropathology and cognitive impairment. We found that mast cell depletion improved contextual fear conditioning in 5XFAD mice without affecting cued fear conditioning, anxiety-like behavior, or amyloid burden. Furthermore, mast cell depletion led to an upregulation of transcriptomic signatures for putatively protective disease-associated microglia and resulted in reduced markers indicative of reactive astrocytes. We hypothesize a system of bidirectional communication between dural mast cells and the brain, where mast cells respond to signals from the brain environment by expressing immune-regulatory mediators, impacting cognition and glial cell function. These findings highlight mast cells as potential therapeutic targets for AD.
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