Sevoflurane Promotes Neurodegeneration Through Inflammasome Formation in APP/PS1 Mice
Abstrak
Sevoflurane (SEVO) is a highly fluorinated methyl isopropyl ether used as an inhalational anesthetic for general anesthesia. Previous studies have shown that SEVO may induce impaired memory and recognition ability and may be associated with neurodegenerative disease, e.g., Alzheimer’s disease (AD). However, the underlying mechanism remains unknown. Here, we used a mouse AD model, APP/PS1, to study the effects of SEVO on neurodegeneration occurring in AD. We found that SEVO exposure significantly impaired the spatial reference memory, sensorimotor, and cognitive function of the mice. Mechanistically, we found that SEVO induced formation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and its downstream caspase 1-mediated production of IL-1β and IL-18, which subsequently deactivated brain-derived neurotrophic factor (BDNF) to promote neurodegeneration. Together, these data suggest that NLRP3 inflammasome is essential for SEVO-induced AD.
Topik & Kata Kunci
Penulis (6)
Guohua Li
Yu Wang
Fang Cao
Dawei Wang
Limin Zhou
Yanwu Jin
Akses Cepat
- Tahun Terbit
- 2021
- Sumber Database
- DOAJ
- DOI
- 10.3389/fnins.2021.647136
- Akses
- Open Access ✓