Effects of leptin on GABA content and receptor expression in hypothalamus of mice with sleep deprivation
10.11855/j.issn.0577-7402.2020.07.05
- VernacularTitle: 瘦素对睡眠剥夺小鼠下丘脑GABA含量及其受体表达的影响
- Author:
Meng-Ting CHEN
1
Author Information
1. Department of Neurorehabilitation, Affiliated Rehabilitation Hospital of Chongqing Medical University
- Publication Type:Journal Article
- Keywords:
GABAA receptor-α1 subtype protein;
Glutamic acid decarboxylase-67;
Sleep deprivation;
] leptin;
γ-aminobutyric acid
- From:
Medical Journal of Chinese People's Liberation Army
2020;45(7):709-713
- CountryChina
- Language:Chinese
-
Abstract:
[Abstract] Objective To observe the effects of the adipocyte hormone leptin on GABA content and receptor expression in hypothalamus of mice with sleep deprivation, and explore the possible mechanisms. Methods Male C57BL/6 mice were randomly divided into three groups (8 each): control group, sleep deprivation (SD) group and leptin supplement (L-SD) group. Mice in control group were set up in a water environment without sleep deprivation, mice in SD group were set up in a "modified multi-platform water environment" to establish a sleep deprivation model, and mice in L-SD group were given leptin 1.3 mg/kg intraperitoneally twice daily in conjunction with sleep deprivation. Seven days after sleep deprivation, the general conditions of mice were observed, body weight was measured and hypothalamic tissues and plasma specimens were collected. ELISA was used to detect the plasma leptin levels, hypothalamic γ-aminobutyric acid (GABA) and glutamate (Glu) contents. Western blotting was performed to detect the expression levels of GABA key glutamate decarboxylase 67 (GAD67) and GABAA receptor α1 subtype protein (GABAARα1). Results Compared with control group, the weight of mice in SD group significantly reduced [(22.03±0.42) g vs. (17.75±0.75) g, P<0.01], while the weight of mice in L-SD group [(15.10±0.38) g] significantly reduced compared with that in control group and SD group (P<0.01). The mice in SD group lost their smooth hair, were particularly sensitive to light and sound, and were slightly manic and aggressive; Compared with control group, the plasma leptin level in mice of SD group significantly reduced [(483.81±21.72) ng/ml vs. (359.14±16.69) ng/ml, P<0.01], and the hypothalamic GABA level significantly reduced [(152.37±8.14) ng/g vs. (111.31±2.96) ng/g, P<0.05]. GABA levels of mice hypothalamus in L-SD group [(132.19±3.38) ng/g] were significantly higher than that in SD group [(111.31±2.96) ng/g, P<0.05], but no statistical difference was when compared with that in control group (P>0.05). The hypothalamic Glu levels were obviously higher in SD group [(686.56±10.01) ng/g] and L-SD group [(668.64+9.93) ng/g] than that in control group [(577.11±16.36) ng/g] (P<0.05), but no statistical significance was found when compared between SD group and L-SD group (P>0.05). The expressive levels of GAD67 and GABAARα1 protein in the hypothalamus of mice in SD group [0.68±0.06, 0.69±0.07] were significantly lower than that in control group (1.09±0.13, 0.99±0.07) (P<0.05); While the expressive levels of GAD67 and GABAARα1 proteins in the hypothalamus of mice in L-SD group (1.39±0.19 and 1.33±0.14, respectively) were significantly higher than those in SD group and control group (P<0.05). Conclusion Leptin can up-regulate the expression of the key GABA synthase GAD67, increase the content of GABA and the expression of GABAARα1 protein in hypothalamus of sleep-deprived mice, which may be an important mechanism of leptin affecting sleep.
