Effects of Rotenone on Cognitive Function as well as Hippocampal Warburg Effect and Microglia Polarization in Rats
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0601
- VernacularTitle:鱼藤酮对大鼠认知功能及其海马Warburg效应和小胶质细胞极化的影响
- Author:
Yu HU
1
;
Hui-ling TANG
2
;
Qing TIAN
2
;
Ping ZHANG
3
;
Wei ZOU
3
;
Xiao-qing TANG
1
Author Information
1. Institute of Clinical Laboratory， The First Affiliated Hospital， University of South China， Hengyang 421001， China
2. Institute of Neuroscience， Hengyang Medical College， University of South China， Hengyang 421001， China
3. Department of Neurology， The Affiliated Nanhua Hospital， University of South China， Hengyang 421001， China
- Publication Type:Journal Article
- Keywords:
rotenone;
Warburg effect;
microglial polarization;
cognitive impairment;
Parkinson's disease
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2021;42(6):801-807
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects of rotenone （ROT） on cognitive function of rats， as well as on Warburg effect and microglia polarization in the hippocampus of rats. MethodsMale Sprague Dawley （SD） rats were randomly divided into ROT-treated group and control group which were subcutaneously injected with ROT （2 mg/kg） and same volume of saline respectively. The cognitive function of rats was evaluated by Y-maze test and novel object recognition （NOR） test. Western blot （WB） was conducted to detect the expression levels of Warburg effect related proteins including hexokinase 2 （HK2）， pyruvate kinase isozyme M2 （PKM2）， pyruvate dehydrogenase kinase 1 （PDK-1）， pyruvate dehydrogenase （PDH）， and lactate dehydrogenase A （LDHA） in the hippocampus， as well as the expression levels of the microglia polarization marker proteins including inducible nitric oxide synthase （iNOS）， arginase-1 （Arg-1）， and chitinase 3-like protein 3 （Ym-1） in the hippocampus. The lactate production and concentration of nitric oxide （NO） in the hippocampus were determined by lactate assay kit and Griess method， respectively. Enzyme-linked immunosorbent assay was used to measure the levels of interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and transforming growth factor β1 （TGF-β1） in the hippocampus. ResultsThe ROT-treated rats showed impaired cognitive function， presented as a significantly lower alternation rate （P < 0.05） in Y-maze test and recognition index （P < 0.001） in NOR test compared with control rats. In the hippocampus of ROT-treated rats， the expressions of HK2 （P < 0.05）， PKM2 （P < 0.01）， PDK-1 （P < 0.05） and LDHA （P < 0.05） were downregulated， The PDH expression was upregulated （P < 0.05）， and the lactate production （P < 0.05） was reduced， indicating that ROT inhibited Warburg effect in the hippocampus of rats. The hippocampus of ROT-treated rats also exhibited increased iNOS expression （P < 0.05）， NO concentration （P < 0.05）， and IL-1β level （P < 0.01）， decreased expression of Arg-1（P < 0.01） and Ym-1 （P < 0.01）， and reduced levels of IL-4 （P < 0.05） and TGF-β1 （P < 0.05）， indicating that ROT promoted M1 polarization of hippocampal microglia. ConclusionROT impairs the cognitive function of rats， inhibits the hippocampal Warburg effect and promotes M1 polarization of hippocampal microglia.
