Targeted inhibition of GABAergic neuron's DRP1 in substantia nigra pars reticulata improves motor function in mice with hepatic encephalopathy
10.16557/j.cnki.1000-7547.2024.01.004
- VernacularTitle:靶向抑制黑质网状部GABA能神经元的DRP1改善肝性脑病小鼠运动功能
- Author:
Xiaodong LI
1
;
Jingjing TIE
;
Jinghao CHEN
;
Yuze SUN
;
Feifei WU
;
Yanling YANG
;
Yayun WANG
Author Information
1. 空军军医大学第一附属医院肝胆胰脾外科,西安 710032
- Keywords:
acute hepatic encephalopathy(AHE);
substantia nigra pars reticulata(SNr);
mitochondria;
dynamic related protein 1(DRP1);
mouse
- From:
Chinese Journal of Neuroanatomy
2024;40(1):25-34
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of mitochondrial division of GABAergic neurons in substantia nigra pars reticulata(SNr)on motor dysfunction in mice with acute hepatic encephalopathy(AHE).Methods:AHE mice model was established by intraperitoneal injection of thioacetamide(TAA).The changes of liver lobules in AHE mice were observed by hematoxylin-eosin(HE)staining.The changes of serum aspartate aminotransferase(AST),alanine aminotransferase(ALT)and blood ammonia in AHE mice were detected by biochemical detection kit.Then,the motor function of AHE mice was observed by rod fatigue test,elevated cross maze test and open field test.Furthermore,the changes of mitochondrial area,perimeter,roundness and other morphological indicators in SNr of AHE mice were ob-served and analyzed by transmission electron microscopy.The expression of mitochondrial division and fusion related molecules in SNr of AHE mice was observed by Western Blot.Then,the expression of mitochondrial dynamic related protein 1(DRP1)in SNr of AHE mice was targeted by AAV virus.The mitochondrial membrane potential(MMP),ATP and reactive oxygen species(ROS)in SNr were detected by fluorescence enzyme marker,and the changes of motor function of mice were observed.Results:Compared with the control group,the motor function of AHE mice was signifi-cantly decreased,the mitochondrial division of SNr was significantly enhanced,and the expression of mitochondrial divi-sion related proteins was significantly increased.The MMP in SNr of AHE mice was significantly decreased,the ATP of cells was decreased,and the ROS was increased.After targeted inhibition of DRP1 expression in SNr of AHE mice,the movement was improved;further observation found that after the mitochondrial division in SNr of AHE mice was inhibi-ted,the MMP was significantly increased,the ATP of cells was increased,and the ROS was decreased,which demon-strated that the mitochondrial function was significantly improved.Conclusion:Targeted inhibition of mitochondrial di-vision of GABAergic neurons in SNr of AHE mice can improve mitochondrial morphology and function,thus alleviating their movement disorders.
