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Decreased hippocampal GLP-1 and the shift in the circadian rhythms are induced by long-term exposure of isoflurane with surgery in mice

Inhalation anesthesia with isoflurane is occasionally associated with the postoperative cognitive impairment and shift in the circadian rhythms. The microglial activation is suggested to be pathogenesis of these complications. Glucagon-like peptide 1 (GLP-1) is specifically expressed in microglia and are associated with circadian transcription factor in hippocampus. We previously reported that hippocampal GLP-1 is reduced with cognitive dysfunction. Therefore, we investigated whether the hippocampal GLP-1 is affected by surgery with inhalation anesthesia. The spatial working memory subjected by spontaneous alteration in the Y-maze is significantly decreased 24 hours in mice with 2h-exposure of isoflurane plus abdominal surgery. In addition, circadian rhythms are significantly shifted during 7 days social isolation after the 2h-exposure of isoflurane with surgery. Western blotting revealed that the protein level of GLP-1 was decreased to the subdetection level for more than three days after the inhalation anesthesia with isoflurane plus abdominal surgery. These results indicate the possibility that the GLP-1 may contribute to the postoperative cognitive dysfunction and shift the circadian rhythms.