| Ketamine as anesthesia analgesic drugs,widely used in clinical anesthesia and anesthesia combination,as anesthetic drugs,the study of its side effects is the key to ensuring the safety of anesthesia,the traditional study on the toxic effects of general anesthetics mainly focus on the body or cells that are directly affected by anesthetics.There are few reports on the nervous system,cognitive impairment,and schizophrenia and hallucinogenic effects.However,pregnancy is a critical period of fetal growth and development,this period of brain cell proliferation and differentiation and synaptic growth,vulnerable to external stimuli damage.In order to accurately understand the harm of ketamine general anesthesia to offspring in the second trimester,this experiment mimic the anesthesia of maternal non-obstetrics in the second trimester,and give the ketamine anesthesia in the middle stage of pregnancy.We select the key proteins and downstream transcription genes as the research object,which are involved in the regulation of Wnt/?-catenin signaling pathway from embryonic development to adult and other life activities,and the complex pharmacological effects of ketamine were discussed at the molecular level.In this study,pregnant rats on gestational day 14,received an anesthetic dose of ketamine intravenously for 3h.The effects of ketamine anesthesia on learning and memory in offspring were observed by a series of behavioral experiments with Odor recognition test(ORT),Contextual and cued Fear Conditioning(CFC)and Morris water maze test(MWM).The nerve density and dendritic spines density of their pups at P30 was examined by Nissl-staining and Golgi staining.The expression of Wnt3 a,Wnt3,Wnt1 a,Wnt7a,?-catenin and GSK-3? m RNA and the expression of the target genes Axnt2,Neurod1,Fosl1,cyclin D1,Tcfe 2a were detected by RT-PCR.The expression of p-?-catenin,GSK-3? and p-GSK-3? in the Wnt/?-catenin signaling pathway were detected by Western Blot.The relationship between the effects of ketamine anesthesia on the hippocampus and the Wnt/?-catenin signaling pathway were investigated by protein and gene.Result: 1.The CFC and MWM tests showed that the ketamine group showed a certain degree of learning and memory impairment.2.The Nissl staining test showed that the neuron density in the hippocampal CA1 and CA3 regions of the ketamine group was significantly decreased(P<0.05).3.The results of Golgi staining showed that the dendritic spine density in hippocampal CA1 region of ketamine group was also significantly decreased(P<0.05).4.The RT-PCR test showed that in the hippocampus Wnt3 a and Wnt7 a m RNA expression were significantly decreased(P<0.05),GSK-3?m RNA expression was significantly increased(P<0.05),and Cyclin D1 and c-myc m RNA were significantly decreased(P<0.05)of the ketamine group.5.The Wentern blot result showed thatGSK-3? protein expression was significantly decreased(P<0.05),p-GSK-3? protein expression was significantly decreased(P<0.05),?-catenin protein expression was significantly increased(P<0.05),and p-?-catenin protein expression was significantly increased(P <0.05)of the ketamine group.In summary,the maternal ketamine anesthesia in the second trimester can lead to the cognitive memory dysfunction of the offspring and the neurotoxicity of the offspring hippocampus leading to neuronal developmental disorder,which may be related to the lower limit of the hippocampus Wnt/?-catenin signaling pathway.And to provide a new idea for the study of the mechanism of general anesthetic and the effect of general anesthetic on learning and memory function. |
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