Role of Cdk5-CRMP pathway in sevoflurane-induced dendritic develop-mental disorder of neurons in prefrontal cortex of neonatal rats / 中国病理生理杂志

ABSTRACT

[ABSTRACT]AIM:Toinvestigatetheeffectofsevoflurane(Sevo)onthedendriticdevelopmentinprefrontal cortex ( PFC) of neonatal rats and the role of cyclin dependent kinase 5 ( Cdk5 )-collapsin response mediator protein ( CRMP) pathway in it.METHODS:Eighty-eight postnatal day 7 Sprague Dawley ( SD) rats were randomly divided into 4 groups (n=22)Air+NS group, Air+roscovitine (Ros) group, Sevo+NS group and Sevo+Ros group.The rats in Air+NS group and Air+Ros group were exposed to the air for 4 h, while the rats in the other 2 groups were exposed to 2.8%sevoflurane for 4 h.The rats received intraperitoneal injection of 150μL normal saline 15 min before exposure in the Air+NS group and Sevo+NS group, while the rats in the Air+Ros group and Sevo+Ros group received intraperitoneal injection of 150μL roscovitine ( in DMSO solution, 10 mg/kg) 15 min before exposure.At the end of exposure, the corti-ces of the rat brain were collected and the protein levels of P35, P25, Cdk5, CRMP1, CRMP2, CRMP4 and p-CRMP2 Ser522 in PFC were detected by Western blot.On the postnatal day 30, the rat brains were sectioned for Golgi-Cox staining and morphological analysis of dendrites in the PFC neurons.Open-field test and contextual fear conditioning test were per-formed on postnatal days 25~27 and 31~32, respectively.RESULTS:Compared with Air+NS group, the expression of P35 in the Sevo+NS group was significantly decreased, and the expression of P25 was dramatically increased (P<0.05), whereas roscovitine partly reversed the changes above induced by sevoflurane (P<0.05).The expression of Cdk5 was not significantly different among all groups.Compared with the Air+NS group, the expression of CRMP1, 2, and 4 in the Se-vo+NS group were decreased, and the protein level of p-CRMP2 Ser522/CRMP2 was increased ( P<0.05 ) , whereas roscovitine partly reversed the changes above induced by sevoflurane (P<0.05), except for the expression of CRMP2. Compared with Air+NS group, the total dendrite length, secondary dendritic length and interactions on 60 and 80 μm shells in the Sevo+NS group were decreased (P<0.01), whereas roscovitine partly reversed the changes above induced by sevoflurane (P<0.05).Compared with Air+NS group, the percentage of freezing time in the Sevo+NS group was de-creased (P<0.01), whereas roscovitine partly reversed the changes induced by sevoflurane (P<0.05).No significant difference among groups in the open-field test was observed.CONCLUSION:Sevoflurane exposure disturbed dendritic de-velopment of neurons in PFC, learning and memory ability of neonatal rats, which may be mediated by Cdk5-CRMP path-way.