Objective To investigate the role of cyclophilin D(CypD)in parvalbumin(PV)in-terneurons in long-term cognitive dysfunction induced by multiple sevoflurane anesthesia in neonatal mice.Methods Thirty-two specific pathogen-free healthy PVCre mice and 32 specific pathogen-free healthy PpifF/F-PVCre mice,aged 6 days,were selected and divided into 4 groups(n=16 each)using a random number table method:control group of PVCre mice(Con group),sevoflurane exposure group of PVCre mice(Sevo group),control group of PpifF/F-PVCre mice(CKO-Con group),and sevoflurane exposure group of PpifF/F-P VCre mice(CKO-Sevo group).Sevo group and CKO-Sevo group were exposed to 3％ sevoflurane for 2 h from the 6th day to the 8th day,while Con group and CKO-Con group inhaled a mixture of 30％ O2 and 70％ air for 2 h at the corresponding time points.On the 42th day of age,the learning and memory abilities of mice in all four groups were evaluated using the novel object recognition test and Morris water maze test.After conducting behavioral experiments,the mice were sacrificed,and hippocampal tissues were collected to determine the expression of PV,CypD,and postsynaptic density protein-95(PSD95)in the hippocam-pus(by Western blot)and to measure the mitochondrial membrane potential(MMP)and activity of reac-tive oxygen species(ROS).Results Compared to Con group,the novel object recognition index was sig-nificantly decreased,the escape latency was prolonged,the time of staying at the original platform quadrant was shortened,the number of crossing the original platform was reduced,the MMP was decreased,the ac-tivity of ROS was increased,the expression of CypD was up-regulated,and the expression of PV and PSD95 was down-regulated in Sevo group(P＜0.05).Compared to Sevo group,the novel object recognition index was significantly increased,the escape latency was shortened,the time of staying at the original platform quadrant was prolonged,the number of crossing the original platform was increased,MMP was increased,the activity of ROS was decreased,the expression of CypD was down-regulated,and the expression of PV and PSD95 was up-regulated in CKO-Sevo group(P＜0.05).There were no statistically significant differ-ences in the novel object recognition index,escape latency,residence time in the original platform quad-rant,the number of crossing the original platform position,MMP,ROS activity and expression of PV and PSD95 among Con group,CKO-Con group and CKO-Sevo group(P＞0.05).Conclusions Up-regulation of CypD expression in PV interneurons is involved in the long-term cognitive dysfunction in neonatal mice sub-jected to multiple sevoflurane anesthesia.
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