Exogenous leptin improves cerebral ischemia-reperfusion-induced glutamate excitotoxic injury in mice by up-regulating GLT-1 and GLAST expression in astrocytes
10.12122/j.issn.1673-4254.2024.06.08
- VernacularTitle:外源性瘦素通过上调星形胶质细胞GLT-1和GLAST的表达减轻小鼠脑缺血再灌注引起的谷氨酸兴奋毒性损伤
- Author:
Jie CHEN
1
,
2
;
Chenxu LIU
;
Chun WANG
;
Li LI
;
Weiting TAO
;
Jingru XUN
;
Honghui TANG
;
Li HUANG
Author Information
1. 蚌埠医科大学 病理生理学教研室,安徽 蚌埠 233000
2. 蚌埠医科大学 心脑血管疾病基础与临床重点实验室,安徽 蚌埠 233000
- Keywords:
leptin;
cerebral ischemia-reperfusion injury;
astrocytes;
glutamate transporter-1;
glutamate-aspartate transporter;
excitotoxicity
- From:
Journal of Southern Medical University
2024;44(6):1079-1087
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.
