Autophagic Degradation Deficit Involved in Sevoflurane-Induced Amyloid Pathology and Spatial Learning Impairment in APP/PS1 Transgenic Mice

Pengcheng Geng, Jiqian Zhang, Wei Dai, Xiaoyu Han, Qilian Tan, Dan Cheng, Panpan Fang, Xuesheng Liu

The adverse effects of anesthetics on elderly people, especially those with brain diseases are very concerning. Whether inhaled anesthetics have adverse effects on Alzheimer's disease (AD), which is the most common form of dementia with brain degenerative changes, remains controversial. Autophagy, a crucial biological degradation process, is extremely important for the pathogenesis of AD. In this study, the inhaled anesthetic sevoflurane elicited many enlarged autolysosomes and impaired the overall autophagic degradation in the hippocampus of an AD mouse model, which is involved in the accumulation of amyloid-β (Aβ) and spatial learning deficits. However, rapamycin treatment counteracted all these effects. The results suggested that inhaled anesthetics may accelerate the pathological process of AD, and enlarged autolysosomes may be a new marker for prediction and diagnosis of the neurotoxicity of anesthetics in AD.