Abdominal Surgery Under Desflurane Exposure During The Late Pregnancy Impair The Learning And Memory Function In Offspring By Regulating Neuronal Dendritic Spines Remodeling Through The Snk-SPAR Signaling Pathway

Object:The aim of this study is to investigate the role of neuronal dendrite spines remodeling regulated by Snk-SPAR signaling pathway in offspring′s cognition impairment induced by abdominal surgery under desflurane exposure during the third trimester.Methods:The pregnant Sprague-Dawley(SD)rats were randomly assigned to control group(C group),desflurane exposure 2hr group(D2 group),desflurane exposure 4hr group(D4 group),desflurane exposure 6hr group(D6 group)and desflurane exposure 4hr combined with abdominal surgery group(D4+S group),with 10 rats in each group.On the 18 th day of gestation,the pregnant rats in D2,D4 and D6 groups received 8%desflurane in 2L/min oxygen for 2hr,4hr or 6hr respectively in a transparent anesthetizing chamber.The D4+S group received exploratory laparotomy under 8%desflurane exposure for 4 hours.The C group received 2L/min oxygen for 6hr.Ability of space perception of offspring was assessed using the Cliff escape experiment on postnatal 7 day(P7).The Open field experiment was used to evaluate their autonomous activities and anxiety-related behaviors on postnatal day 22(P22).Spatial learning and memory function of offspring were tested by the Morris Water Maze(MWM)on postnatal day 30(P30).The day after the MWM test,hippocampal tissues of offspring were harvested.The density and type of dendritic spines in CA1,CA3,DG of hippocampus were detected by Golgi-cox staining.Snk,SPAR,and PSD-95 transcript and protein levels were measured in rat offspring hippocampal tissues using real-time PCR(RT-PCR)and Western Blot,respectively.Results:There were no significant differences in the Cliff escape experiment and the Open field test between the five groups(P > 0.05).MWM test results showed that compared with the C group,the escape latency of the offspring in the D4+S group was significantly increased(P < 0.05),the platform-crossing times,target quadrant traveling time and swimming speed showed no significant differences(P > 0.05).Golgi-cox staining results showed that compared with the C group,the density of dendritic spines and the proportion of mushroom spines in hippocampus CA1 region of offspring in the D4+S group were decreased(P<0.05),the density of dendritic spines in DG region was significantly decreased(P<0.05),but the types of dendritic spines showed no differences in DG region(P > 0.05).There were no changes in CA3 region.Compared with the C group,the level of Snk protein was increased in the D4+S group(P<0.05),the expression of SPAR and PSD-95 protein were decreased(P<0.05).Compared with C group,the level of Snk m RNA in the D4+S group was increased(P < 0.05),and the expression of SPAR and PSD-95 m RNA were significantly decreased(P<0.05).There were no significant differences in the above indexes between the desflurane exposure group(D4 group)and the C group(P > 0.05).Conclusion:Taken together,the results in the present study suggested that desflurane exposure in the late pregnancy had no effect on cognition,but abdominal surgery under desflurane exposure impair learning and memory function in offspring rats by activating the expression of Snk,then inhibiting SPAR and PSD-95 expression,thus affecting the development of dendritic spines in neurons-hippocampal.This indicated that Abdominal surgery under desflurane exposure during the late pregnancy impair the learning and memory function in offspring by regulating dendritic spines remodeling through the Snk-SPAR signaling pathway.