Mechanism of clonidine preventing sevoflurane-induced neurotoxicity in neonatal mice: relationship with Tau phosphorylation
10.3760/cma.j.cn131073.20231120.00408
- VernacularTitle:可乐定预防七氟烷对新生小鼠脑神经毒性的机制：与Tau蛋白磷酸化的关系
- Author:
Xu WANG
1
;
Mingyang SUN
;
Jiaqiang ZHANG
;
Shuang ZENG
Author Information
1. 河南省人民医院（郑州大学人民医院）麻醉与围术期医学科，郑州 450003
- Keywords:
Clonidine;
Sevoflurane;
Tau phosphorylation
- From:
Chinese Journal of Anesthesiology
2024;44(4):424-427
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the relationship between the mechanism of clonidine preventing sevoflurane-induced neurotoxicity and Tau phosphorylation in neonatal mice.Methods:Seventy-two SPF healthy newborn C57BL/6 wild-type mice, aged 6 days, were divided into 4 groups ( n=18 each) using a random number table method: normal control group (C group), clonidine control group (CC group), sevoflurane-induced neurotoxicity group (S group) and prevention with clonidine group (SC group). Mice inhaled 3% sevoflurane for 2 h daily on postnatal days 6, 9 and 12, and normal saline or clonidine 1 mg/kg was intraperitoneally injected before anesthesia in S group and SC group. Six mice were randomly selected from each group after the end of anesthesia on postnatal day 12, and the hippocampal tissues were removed for determination of the expression of the phosphorylated Tau protein (AT8) and total Tau protein (Tau46) at Tau-PS202 and Tau-PT205 sites by Western blot. The ratio of AT8 expression to Tau 46 expression (AT8/Tau46 ratio) was calculated. Another 12 mice in each group underwent novel object recognition test on postnatal days 29-30 (the discrimination ratio of novel objects was observed), and the Morris water maze test was performed on postnatal days 31-37 (the escape latency and the times of crossing the platform were observed). After the end of the behavioral testing, the hippocampal tissues were harvested under anesthesia to detect the expression of postsynaptic density-95 (PSD-95) by Western blot. Results:Compared with group C, the expression of AT8 was significantly up-regulated, the ratio of AT8/Tau46 was increased, the expression of PSD-95 was down-regulated, and the number of crossing platforms and novel object discrimination ratio were decreased in group S ( P<0.05). Compared with group S, the expression of AT8 was significantly down-regulated, the ratio of AT8/Tau46 was decreased, the expression of PSD-95 was up-regulated, and the number of crossing platforms and novel object discrimination ratio were significantly increased in group SC ( P<0.05). There was no significant difference in the expression of Tau46 and escape latency among the four groups ( P>0.05). Conclusions:The mechanism by which clonidine prevents sevoflurane-induced neurotoxicity in neonatal mice is related to the inhibition of Tau phosphorylation.
