Effects and mechanisms of isoflurane on anxiety and cognitive function in offspring of maternal sleep deprived mice
Objective:To investigate the effects of isoflurane exposure in infancy on anxiety and cognitive functions in adult offspring mice of maternal sleep deprivation(MSD),and the mechanisms in it.Methods:32 healthy c57BL/6J pregnant mice were divided into 4 groups(n=8)using the random number table method:a control group(Con group),a maternal sleep deprivation group(MSD group),an isoflurane exposure of neonatal offspring mice group(Con-ISO group),and a maternal sleep deprivation+isoflurane ex-posure of neonatal offspring mice group(MSD-ISO group).Pregnant mice in the MSD group and the MSD-ISO group were subjected to sleep deprivation(12:00～18:00)for7 consecutive days from day15 to day21 of gestation,while pregnant mice in the Con group and the Con-ISO group were not subjected to sleep deprivation.The neonatal offspring mice in the Con-ISO group and the MSD-ISO group were exposed to 1.5%isoflurane for 6h,and neonatal offspring mice in the Con group and the MSD group were exposed to 100%oxy-gen for 6 hours.On postnatal 90 day,the offspring mice were evaluated for anxiety using the open field test and elevated plus maze test,and the offspring mice were analyzed for learning and memory ability using the Morris water maze test.The levels of interleukin(IL)-6,IL-1β and tumor necrosis factor(TNF)-α in hippocampal tissues of offspring mice were measured by enzyme linked immu-nosorbent assay.Results:Compared with the Con group,the time spent in and the number of entries into the central area,the time spent in and the number of entries into the open arms,the percentage of target quadrant swimming distance and the time of swimming in the target quadrant,the number of crossing the platform,and the levels of hippocampal inflammatory factors IL-1β,IL-6 and TNF-α were decreased,while the swimming distance covered was increased in the CON-ISO group,the MSD group and the MSD-ISO group(P<0.05).Compared with the Con-ISO group and the MSD group,the time spent in and the number of entries into the central area,the time spent in and the number of entries into the open arms,the percentage of target quadrant swimming distance and the time of swimming in the target quadrant,the number of crossing the platform,and the levels of hippocampal inflammatory factors IL-1β,IL-6 and TNF-α were further decreased,while the swimming distance covered was further increased in the MSD-ISO group(P<0.05).The levels of hippocampal inflammatory factors IL-1β,IL-6 and TNF-α were negatively correlated with the time spent in and the number of entries into the central area,the time spent in and the number of entries into the open arms,the percentage of target quadrant swimming distance and the time of swimming in the target quadrant,the number of crossing the platform in the Con-ISO group,the MSD group and the MSD-ISO group.However,the distance swimming distance covered was positively correlated with that of the Con-ISO group,the MSD group and the MSD-ISO group(P<0.05).Conclusion:Infant isoflurane exposure aggravated anxiety and cognitive function impairment in adult offspring of maternal sleep deprivation,and the mechanism may be related to increased inflammatory factors.
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