Study On The Mitochondrial Dysfunction Of Astrocytes Caused By The Loss Of Fars2 Gene Function And Its Related Mechanism

Objective:The FARS2 gene can encode mitochondrial phenylalanyl-t RNA synthetase,which belongs to mitochondrial aminoacyl-t RNA synthetase,which controls the binding of t RNA and its cognate amino acid,thus playing an important role in translation initiation.In the previous research work of our group,it was verified in vitro that Fars2 gene mutation can cause changes in mouse brain neurons,including the number of neurons,axonal length,survival,and reactive oxygen species content.And it was observed that the expression level of the Fars2 gene in mouse astrocytes was higher than that in neurons.Therefore,it is an important topic for us to study the influence of the Fars2 gene on astrocyte function and the change of intracellular mechanisms.Methods:This topic uses to construct a vector containing the FARS2 gene,and study the localization of FARS2 in cells through subcellular localization technology,confirming that FARS2 gene mutants can be localized in mitochondria,and further study the relationship between gene mutation and mitochondria;Analysis The expression of Fars2 in neurons and astrocytes of mice and the regularity of its expression were studied;The abnormal mechanism of astrocyte dysfunction caused by the Fars2 gene mutation was analyzed,including changes in mitochondrial function and inflammatory factors,etc.To further verify the effect of astrocyte dysfunction on neuronal activity.Result:1.The FARS2 gene is highly expressed in astrocytes of the mouse cerebral cortex.The protein encoded by the FARS2 gene is expressed in mitochondria,and it is still expressed in mitochondria after homozygous mutation of FARS2.2.sh RNA-Fars2 can lead to astrocyte dysfunction in the cerebral cortex,including decreased GFAP protein expression,increased apoptosis and autophagy,altered expression of inflammatory factors,and inhibited c GAS-STING pathway proteins.3.The fragmentation of mitochondrial morphological cristae,the increase of ROS,the decrease of ATP content,the change of mitochondrial copy number and oxidative respiratory chain complex,and the imbalance of mitochondrial dynamic homeostasis can lead to mitochondrial dysfunction.4.A co-culture system of neurons and astrocytes was constructed to analyze the effect of astrocytes on neuronal neurons.When the Fars2 gene in astrocytes was knocked down,it could affect the activity of neurons,and intracellular ROS changes and neuronal apoptosis affect the normal function of neurons.Conclusion:Homozygous mutations in the Fars2 gene can lead to mitochondrial dysfunction in astrocytes,thereby affecting the function of neurons.Maintaining the normal physiological functions of astrocytes is expected to be a target for the treatment of neurological diseases.