| First Author | Lin CJ | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 9 | Pages | 113141 |
| PubMed ID | 37713312 | Mgi Jnum | J:341732 |
| Mgi Id | MGI:7538766 | Doi | 10.1016/j.celrep.2023.113141 |
| Citation | Lin CJ, et al. (2023) Mast cell deficiency improves cognition and enhances disease-associated microglia in 5XFAD mice. Cell Rep 42(9):113141 |
| abstractText | 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. |
