Overexpression Of PGC-1? Protect Mitochondrial Function Of C57BL Mouse Induced By MPTP

Background Parkinson disease(PD)is an adult onset neurodegenerative disease characterized by a-synuclein neuropathology and progressive dopaminergic neuronal loss in the substantia nigra pars compacta(SN).Mitochondrial dysfunction and oxidative stress are intricately linked to PD pathogenesis.PGC-1?(peroxisome proliferator-activated receptor 1 alpha),a multifunctional transcription factor,is a key regulator of mitochondrial biogenesis and cellular energy metabolism.It controls oxidative phosphorylation,antioxidant defense and autophagy.Its pathways controlling mitochondrial activity rapidly emerge as potential therapeutic targets..Currently there are partly research on the role of PGC-1? in the neurodegenerative disease,only a few studies have addressed PGC-1a in the context of PD,and its relevance for PD is poorly understood.Objective 1.Implement the overexpression of PGC-1? gene in SN region of C56BL/6 mice through lentivirus injection.2.Study the effects of overexpression of PGC-1? gene in mitochondria of animal models for PD.Methods 1.Establishment of the animal model: Based on the applicable lentivirus MOI and protocol of MPTP injection from preliminary tests,we modeled the PGC-1? overexpression animals and PD animals.2.Rotarod test and eleaveted body swing test were employed to access the motor changes of mice before and after experimental interventions.3.Electron microscopy were employed to observe the mitochondria structure of mice in groups.4.The level of SOD in SN region of C57BL/6 mice was evaluated by WST-1.5.WB and Real-time PCR were used to evaluate the PGC-1? level in groups.6.The expression of TH in SN region of C57BL/6 mice was tested by both immunohistochemistry and WB.Results 1.WB and PCR respectively showed the protein level and the transcriptional level of PGC-1? in group P+M were significantly increased than those in group L+M,validating the overexpression of PGC-1? level in SN region of C56BL/7 mice.2.Results of both Rotarod test and eleaveted body swing test demonstrated the improvement of motor behavior and body rigidity in group P+M,compared with group M,E+M,L+M.3.Evaluation of TH expression by immunohistochemistry and WB showed the higher level in the SN region of group P+M than group L+M.4.Assessment of SOD level by WST-1 found a rising trend of SOD in SN region after the overexpression of PGC-1? when compared with group L+M.5.Observation from transmission electron microscopy showed normal mitochondria with defined mitochondrial crests in group NS;the mitochondria in group M displayed several abnormalities,as swelling,cristae disruption and internal vesicles;the mitochondria in group M+P showed less demage than group M..Conclusions 1.The infection of Lentivirus to the DA neurons could be highly efficient and LV-GFP-PGC-1? Lentivirus successfully fulfilled the overexpression of PGC-1? in SN region of mice,making it possible to further probe the effect of PGC-1? in PD mice model.2.Overexpression of PGC-1? could restore the damage of DA neurons,improve both the impairment of motor coordination and abnormal behavior of high muscular tension.3.Overexpression of PGC-1? could also be beneficial to resist the he MPTP-induced mitochondria lesion by stimulating the production of SOD and promoting the ROS detoxification.4.Overexpression of PGC-1? play can reduce the death of dopaminergic neurons in SN region of C56BL/7 mice by protecting the structure and function of mitochondria.