Role of autophagy in cognitive decline caused by sevoflurane anesthesia in aged mice: the relationship with neurogenesis

Objective To evaluate the role of autophagy in cognitive decline caused by sevoflurane anesthesia and the relationship with neurogenesis in aged mice. Methods Forty-five healthy SPF male mice, aged 20-22 months, weighing 25-35 g, were divided into 3 groups (n=15 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S) and autophagy agonist rapamycin group (group R). Rapamycin 0.2 mg/kg was intraperitoneally injected every day for 7 days in group R, while the equal volume of solvent dimethyl sulfoxide was given instead in S and C groups.In group S and group R, 3% sevoflurane was inhaled for 2 h once a day for 3 consecutive days starting from 5th day of administration, while the mixture of air and oxygen was inhaled instead in group C. Five mice in each group were randomly selected after the last anaesthesia and sacrificed, and the hippocampus was removed for determination of the expression of microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) and Beclin-1 by Western blot.The other mice were sacrificed after Morris water maze test was performed, and hippocampi were isolated for determination of doublecortin (DCX) positive cells in the dentate gyrus by immunohistochemistry. Results Compared with group C, the escape latency was significantly prolonged, the percentage of time spent in the target quadrant was decreased, the expression of LC3Ⅱ and Beclin-1 was down-regulated, LC3Ⅱ/LC3Ⅰ ratio was decreased, and DCX positive cell counts were reduced in S and R groups (P<0.05). Compared with group S, the escape latency was significantly shortened, the percentage of time spent in the target quadrant was increased, the expression of LC3Ⅱ and Beclin-1 was up-regulated, LC3Ⅱ/LC3Ⅰ ratio was increased, and DCX positive cell counts were increased in group R (P<0.05). Conclusion Autophagy is involved in the process of cognitive decline caused by sevoflurane anesthesia, which is related to inhibiting neurogenesis in the hippocampus of aged mice. Key words: Autophagy; Anesthetics, inhalation; Aged; Cognition disorders; Neurogenesis