Social isolation is suggested to be a detrimental for the confusional states and abnormal interaction with cognitive impairment after the isoflurane plus surgery. However, the underlying mechanisms of these states remain unclear. After 2 hours exposure of isoflurane with abdominal surgery followed by social isolation for 24 h (ISO+SI-24h), the spontaneous alternations in Y-maze in male mice (7-10 weeks old) was significantly decreased, indicating that the spatial working memory was impaired by ISO+SI-24h. In general, only raring the 7-days of SI without the surgery, mice exhibit normal behaviors. However, the exposure of isoflurane with abdominal surgery in mice followed by raring 7 days of SI enhanced the mounting and sniffing behaviors against intruder mice in the home cage. In addition, the protein level of hippocampal dopamine D 2 receptors, but not prefrontal cortex was significantly decreased in mice with isoflurane plus surgery and SI. Since D 2 receptor is important for the cognitive function and psychosocial, these results imply the possibility that decrease in D 2 receptor contribute to the postoperative abnormal social interaction and cognitive dysfunction.
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. Glucagonlike 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 2hexposure 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.
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