The mechanism of cognitive dysfunction induced by sevoflurane and the Tau/tubulin tyrosine like ligase 6/Spastin signaling pathway in young rats
Objective To explore whether the inhaled anesthetic sevoflurane after repeated exposure causes dendritic spine remodeling of neuronal neurons in young mice through the Tau/tubulin tyrosine like ligase 6(TTLL6)/microtubule dissecting protein(Spastin)signaling pathway.Methods A total of 44 juvenile[postnatal 6 d(P6)]and adult[postnatal 60 d(P60)]mice were selected.According to the random number table method,the mice were divided into four groups(n=11):a juvenile control group(the P6con group),a juvenile anesthesia group(the P6sevo group),an adult control group(the P60con group)and an adult anesthesia group(the P60sevo group).The P6sevo and P60sevo groups were administered with 3％sevoflurane+60％oxygen for 3 d,2 h/d;while the P6con and P60con groups were given 60％oxygen for 3 d,2 h/d.On the day after molding,mouse hippocampus tissue was collected to detect the levels of postsynaptic dense protein 95(PSD95),Tau,TTLL6 and Spastin by Western blot.The expression of Tau,TTLL6 and Spast-in,and the co-location of Tau and TTLL6 were detected by immunofluorescence.Results Compared with the P6con group,the P6se-vo group showed decreases in the levels of hippocampal PSD95(P＜0.05),and increases in the levels of Spastin(P＜0.05),without statis-tical difference in Tau and TTLL6 expression(both P＞0.05).There was no statistical difference in hippocampal PSD95,Tau,TTLL6 and Spastin levels between the P60con group and the P60sevo group(all P＞0.05).The results of immunofluorescence staining showed that Tau and TTLL6 were co-localized in the P6con group and the P6sevo group,while the co-localization of Tau and TTLL6 in the hip-pocampal tissue of the P60con and P60sevo groups was not obvious.Compared with the P6con group,repeated exposure to sevoflurane resulted in remarkable increases in the number of Tau-,TTLL6-and Spastin-positive cells in the hippocampus of the P6sevo group(all P＜0.05).The above changes were not significantly in adult mice(P＞0.05).Conclusion Sevoflurane causes dendritic spine remodel-ing in young rat neurons through the Tau/TTLL6/Spastin signaling pathway.
SevofluraneCognitive disorderDendritic spineTauTubulin tyrosine like ligase 6SpastinMouse
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