Sevoflurane and Aβ1-42 Oligomers Synergistically Induce Morphological Changes of Astrocytes in the Hippocampus of Male Mice.

Abstract

Background: Reactive gliosis serves as a characteristic feature of the pathophysiology of Alzheimer's disease (AD). Nevertheless, the influence of anesthetics on the morphological dynamics of astrocytes remains ambiguous.

Methods: Employing ex vivo hippocampal slices, in this study, we explored the impacts of sevoflurane and Amyloid-β peptide 1-42 (Aβ_1-42) oligomers on astrocytic morphology. The primary outcomes encompassed the fluorescence intensity of glial fibrillary acidic protein (GFAP), the levels of a 38-kDa GFAP breakdown product (a marker of astroglial injury), and quantitative morphometric analyses (cell volume, surface area, branch complexity, and Sholl intersections).

Results: Co-exposure to sevoflurane and Aβ_1-42 led to an elevation of the 38-kDa GFAP breakdown product and a significant reduction in the mean fluorescence intensity of GFAP. Moreover, it resulted in a decrease in astrocytic volume, surface area, branch complexity, and Sholl intersections. These synergistic alterations were not observed when either treatment was administered alone.

Conclusions: These findings imply that sevoflurane aggravates Aβ_1-42-induced astrocytic dysfunction, which has implications for perioperative management in patients with AD or those at risk of developing AD.