Prolonged Volatile Anesthetic Exposure Exacerbates Cognitive Impairment and Neuropathology in the 5xFAD Mouse Model of Alzheimer's Disease.

Abstract

BACKGROUND:

Alzheimer's disease (AD) is a progressive neurodegenerative disease which shows a set of symptoms involving cognitive changes and psychological changes. Given that AD is the most common form of dementia in aging population and the increasing demand for anesthesia/surgery with aging, there has been significant interest in the exact impact of volatile anesthetics on cognitive function and pathological alterations in AD population.

OBJECTIVE:

This study aimed to investigate behavioral changes and neuropathology in the 5xFAD mouse model of Alzheimer's disease with short-term exposure or long-term exposure to desflurane, sevoflurane, or isoflurane.

METHODS:

In this study, we exposed 5xFAD mouse model of AD to isoflurane, sevoflurane, or desflurane in two different time periods (30 min and 6 h), and the memory related behaviors as well as the pathological changes in 5xFAD mice were evaluated 7 days after the anesthetic exposure.

RESULTS:

We found that short-term exposure to volatile anesthetics did not affect hippocampus dependent memory and the amyloid-β (Aβ) deposition in the brain. However, long-term exposure to sevoflurane or isoflurane significantly increased the Aβ deposition in CA1 and CA3 regions of hippocampus, as well as the glial cell activation in amygdala. Besides, the PSD-95 expression was decreased in 5xFAD mice with exposure to sevoflurane or isoflurane and the caspase-3 activation was enhanced in isoflurane, sevoflurane, and desflurane groups.

CONCLUSION:

Our results demonstrate the time-dependent effects of common volatile anesthetics and implicate that desflurane has the potential benefits to prolonged anesthetic exposure in AD patients.

• Authors: Fanglei Han, Jia Zhao, Guoqing Zhao
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 84 Issue 4 Pg. 1551-1562 ( 2021) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 34690137 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Inhalation
• Sevoflurane
• Isoflurane

Topics

• Alzheimer Disease (pathology)
• Anesthetics, Inhalation (adverse effects, pharmacology)
• Animals
• Cognitive Dysfunction (chemically induced)
• Disease Models, Animal
• Hippocampus (pathology)
• Isoflurane (adverse effects, pharmacology)
• Maze Learning
• Mice
• Mice, Transgenic
• Neuropathology
• Sevoflurane (adverse effects, pharmacology)
• Time Factors