Mechanism of aucubin improving attention deficit hyperactivity disorder induced by maternal exposure to S-ketamine in offspring mice: GABAergic neurons in habenular nucleus
10.3760/cma.j.cn131073.20240314.00808
- VernacularTitle:桃叶珊瑚苷改善孕期艾司氯胺酮暴露诱发子代小鼠注意缺陷多动障碍的机制：缰核GABA能神经元
- Author:
Gege LYU
1
;
Caoyuan MA
;
Yudong SHAN
;
Zhifang YU
;
Limin ZHANG
;
Wei ZHANG
Author Information
1. 郑州大学附属第一医院麻醉科，郑州 450052
- Keywords:
Attention deficit disorder with hyperactivity;
Ketamine;
Aucubin;
GABAergic neuron;
Habenula
- From:
Chinese Journal of Anesthesiology
2024;44(8):941-945
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the relationship between the mechanism by which aucubin improved attention deficit hyperactivity disorder (ADHD) induced by maternal exposure to S-ketamine and GABAergic neurons in the habenular nucleus of offspring mice.Methods:SPF healthy C57BL/6 wild-type pregnant mice were used in this study, and an ADHD model in offspring mice was established by intraperitoneally injecting S-ketamine in the middle and late pregnancy. Twenty-four offspring of pregnant mice exposed to S-ketamine were divided into 2 groups ( n=12 each) at 14 days after birth using a random number table method: ADHD + normal saline group (AN group) and ADHD + aucubin group (AA group). Twenty-four offspring of pregnant mice exposed to normal saline were divided into 2 groups ( n=12 each) at 14 days after birth by a random number table method: control + normal saline group (CN group) and control + aucubin group (CA group). Aucubin 40 mg/kg was intraperitoneally injected once a day for 7 consecutive days in CA group and AA group, and the equal volume of normal saline was given instead in CN group and AN group. At 14 days after birth, the 16-channel microfilament array electrode was placed in the habenular nucleus, and the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was recorded when the mice buried beads in the marble burying test. At 21 days after birth (after the end of peritoneal administration), the impulsive and stereotypical behaviors of offspring mice were evaluated by elevated zero maze and marble burying test, respectively, and then the expression of glutamate decarboxylase 2 (GAD2) in habenular nucleus was detected by the immunofluorescence method. Results:Compared with CN group, the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was significantly increased, the expression of GAD2 was down-regulated, the time spent in the open arm was prolonged, the number of entries into the open arm and the number of buried beads were increased in AN group ( P<0.05), and no statistically significant differences were found in the above indexes in CA group ( P>0.05). Compared with AN group, the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was significantly decreased, the expression of GAD2 was up-regulated, the time spent in the open arm was shortened, and the number of entries into the open arm and the number of buried beads were decreased in AA group ( P<0.05). Conclusions:The mechanism by which aucubin alleviates prenatal S-ketamine exposure-induced ADHD may be related to increasing the number of GABAergic neurons in the habenular nucleus of offspring mice.
