Abstract
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.
Highlights
Alzheimer’s disease (AD) is the most common form of dementia with brain degenerative changes, which is highly prevalent in the elderly population (Querfurth and LaFerla, 2010)
The inhaled anesthetic sevoflurane led to amyloid peptide accumulation due to abnormalities in autophagy degradation machinery, which in turn caused spatial learning impairment in APP/PS1 transgenic mice
Autophagy inducer rapamycin could counteract these effects. These results revealed that inhaled anesthetics may accelerate the pathological process of AD, reminding anesthesiologists to pay close attention to the use of inhaled anesthetics in patients with AD during clinical practice
Summary
Alzheimer’s disease (AD) is the most common form of dementia with brain degenerative changes, which is highly prevalent in the elderly population (Querfurth and LaFerla, 2010). Due to its advantages of rapid onset, strong controllability, and fewer side effects, inhaled anesthesia has become the most common method of general anesthesia. Growing evidence revealed that the aged brain is vulnerable to inhaled anesthetics (Vutskits and Xie, 2016), for example, isoflurane, sevoflurane and desflurane can impair the cognitive function of older rodents (Culley et al, 2003; Le Freche et al, 2012; Li et al, 2014; Callaway et al, 2015). Several studies have demonstrated that inhaled anesthetic isoflurane could impair spatial learning of AD mouse model (Li et al, 2014), while other studies have shown that isoflurane and desflurane
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