Sevoflurane rescues the eletroretinogram of AD transgenic Drosophila
Chia-Wen Chen1,2,Wei-Yong Lin3, Yih-Shyuan Wu4, Kuen-Bao Chen1, Hsin-Ping Liu5, Yu-Cheng Kuo6,7, Chi-Yuan Li1,2
1Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan
2Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
3Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
4Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan
5Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan
6Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan
7Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan
Background
The clinical features of Alzheimer’s disease (AD) are mental functions loss such as learning and memory. However, changes in retina are earlier than memory problems in AD. In vivo study, AD- related retinal abnormalities may be associated with the deposition of β-amyloid protein (Aβ) in retina. Recent data suggest that inhalational anesthetics, such as sevoflurane, might cause neurodegeneration, but the effect on photoreceptor neurons is unclear. In our study, we investigate the effect of sevoflurane on the photoreceptor neurons of AD transgenic Drosophila.
Methods
We used five to six-day-old AD transgenic male flies (elav/Y;H29.3/+) and control male flies (elav/Y) (n=6). AD flies were exposed with 2.1% sevoflurane for 1 hour per time. After 4 and 16 times of exposure, all flies were analyzed with electroretinogram (ERG) assay. The amplitude of the light on /off transient was calculated as the difference (△ERG) between the highest voltage reached after lights on/off and this baseline value. Data are presented mean ± SE. Differences between mean values were evaluated using one-way ANOVA with supplementary Fisher’s LSD (Least Significant Difference) method. Statistical significance was set at p < 0.05.
Results
Expression of Aβ42 in Drosophila neurons including retina neurons decreased the light-evoked visual response compared with controls (Figure A and C, p<0.05 and p<0.001, respectively). Sevoflurane reverted the △ERG of AD flies to the similar level as controls after exposure for 4 times (Fig A, p<0.01). The similar effect on AD flies after exposure for 16 times was also found (Fig C, p<0.001) and the △ERG is higher than controls (Fig C, p<0.01). ERG traces revealed a decreased amplitude of depolarization of photoreceptors indicated phototransduction defects. These ERG defects could be
rescued with 2.1% sevoflurane.
Conclusion
Our study revealed that 2.1% sevoflurane rescued the ERG of AD transgenic Drosophila. In general anesthesia, sevoflurane has been proved could enhance the inhibitory signals of GABAA receptors, which were expressed in the medulla of Drosophila visual system. In conclusion, our findings suggest that sevofluane may ameliorate retinal abnormalities of AD through enhancing the inhibition effect of GABAA receptors.
Keywords: Sevoflurane, electroretinogram, Alzheimer’s disease, GABAA receptor, Drosophila.
