Inhalational Anesthetic Sevoflurane Rescues Retina Function in Alzheimer’s Disease Transgenic Drosophila

Chia-Wen      Chen; Wei-Yong      Lin; Kuen-Bao      Chen; Yih-Shyuan      Wu; Yu-Cheng      Kuo; Hsin-Ping      Liu; Chi-Yuan      Li

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease that is a great public health problem worldwide. The cause and mechanism of AD are not well understood. Inhalational anesthetics have been suggested to induce neurotoxicity, leading to memory deficits and the progression of AD. However, recent data have shown that inhalational anesthetics may protect against neurotoxicity and are not associated with an increased risk of AD. We used a Drosophila model to directly investigate the neurologic effects of the inhalational anesthetic sevoflurane on AD. Five- to six-day-old control and AD-transgenic flies were exposed to 2.1% or 3% sevoflurane 4 and 16 times for 1 hour each time. Electroretinograms (ERG), retinal immunohistochemistry, climbing ability, and survival were analyzed after sevoflurane treatment. The data were evaluated using Student’s t-test or a one-way ANOVA with a supplementary Fisher’s LSD (Least Significant Difference) test. Statistical significance was set at p<0.05. The ΔERG, climbing ability, and survival were lower in ADtransgenic flies. Exposure to 2.1% sevoflurane 4 and 16 times and to 3% sevoflurane 16 times rescued the ΔERG in ADtransgenic flies. Sevoflurane exposure did not attenuate the climbing ability or survival of control and AD-transgenic flies. The inhalational anesthetic sevoflurane might not have exerted neurotoxic effects on control and AD-transgenic flies; in fact, sevoflurane might confer selective neuroprotection on the retinal function of AD-transgenic flies. These results suggest the need for future studies to determine the potential effects of anesthetics on AD-associated neuroprotection or neurotoxicity.

Keywords: Alzheimer’s disease, β-amyloid protein, Drosophila, inhalational anesthetics, sevoflurane