| Objective:Sleep deprivation(SD)compromises learning and memory in both humans and animals.Sleep deprivation may have cumulative effects resulting in decreased hippocampal cell proliferation,cell survival,and neurogenesis,which may result in the deterioration of memory.Isoflurane is one of the commonly used anesthetics in the operating room,long term exposure to volatile anesthetics can lead to neurodegeneration in the developing animal brain and its effect on cognitive function is not clear.The PI3K/AKT signaling pathway has been shown to play an important role in the amelioration of neurodegenerative diseases,and its critical role in neuronal development,survival,and death is also widely known.Dexmedetomidine(DEX),anα-2 adrenergic agonists,which have been developed for clinical anesthesia and sedation.In recent years,the neuroprotective effects of DEX have been demonstrated.In this study,we used a modified multiple platform method to establish a rat model of sleep deprivation to explore whether DEX,as a pre anesthetic drug,could exert a neuroprotection and its possible mechanism through the PI3K/AKT pathway in cognitive dysfunction.Methods:1.Experimental groups and model establishment:6-week-old male Sprague Dawley rats were randomly divided into 7 groups:Control group(Control),Sleep deprivation(SD),Isoflurane(ISO),SD+ISO,DEX+SD+ISO,LY294002+SD+ISO(L+SD+ISO),DEX+LY294002+SD+ISO(D+L+SD+ISO).The control group had no operation.The sleep deprivation group underwent sleep deprivation for 48 hours.The isoflurane group inhaled 1.1%isoflurane for 3 hours.After 48 hours of sleep deprivation,the SD+ISO group inhaled 1.1%isoflurane for 3 hours.DEX and LY294002 were given(20μg/kg),LY294002(25μg/kg).2.Observation of cognitive impairment in the perioperative period:The effect of sleep deprivation or isoflurane on the learning and memory ability of rats was evaluated by Morris water maze(MWM),and the frequency of a single rat passing through the platform area and the time in the target quadrant were recorded as Spatial memory ability index,comparison between groups to evaluate the effects of isoflurane and sleep deprivation3.PI3K-AKT pathway,apoptosis and therapeutic effect of DEX after sleep deprivation:LC3B expression level changes in the hippocampus were detected by immunohistochemical staining,and the expression levels of PI3K/AKT pathway and apoptosis related proteins(LC3B,P62 and Beclin-1)in the hippocampus were detected by Western Blot.Results:1.After isoflurane inhalation in sleep-deprived rats,cognitive dysfunction in rats was observed and the model was successfully established.2.Rats in the SD+ISO group crossed the hidden platform less times and stayed in target quadrant for a shorter time in contrast with that in the control group.The expression of LC3B in neurons was enhanced markedly,PI3K and AKT phosphorylation levels were decreased,LC3B,P62 and Beclin-1 expression were increased compared with that in the control rats.3.Compared with the SD+ISO group,the number of crossing the platform and the time spent in the target quadrant were increased,the expression of autophagosomes was inhibited,the phosphorylation levels of PI3K and AKT were increased,the expression of LC3B,P62 and Beclin-1 was decreased.DEX attenuate the cognitive impairments of sleep—deprived rats.This ameliorative effect could be inhibited by PI3K inhibitors.Conclusion:1.Isoflurane can induce cognitive dysfunction in sleep-deprived rats.DEX can significantly improve cognitive dysfunction induced by isoflurane,reduce autophagy,and alleviate pathological changes in hippocampus2.DEX may participate in the regulation of excessive autophagy and apoptosis through the PI3K/AKT pathway,enhance protein phosphorylation,inhibit hippocampal cell apoptosis,and play a protective role in the brain... |
PDF Full Text Request