Mechanisms Of Vitamin B3 Protection In The PINK1 Mutant Drosophila Model Of Parkinson’s Disease

Objective:To investigate the potential mechanism of vitamin B3 on a classical in Parkinson’s disease（PD）transgenic drosophila model with PINK1 mutation--PINK1^B9,and clarify the protective effect of vitamin B3 by observing morphological development and creeping ability of PD transgenic drosophila,as well as impacts on dopamine（DA）neurons.Methods:In this study,MHC-GAL4 and TH-GAL4 two specific promoters are used to induce PINK1^B9 specifically expression in drosophila muscle and DA neurons to establish the GAL4/UAS system model of PD transgenic drosophila model.Those were divide into 3groups:Normal control group:the wild type（WT）;PD model group:PINK1^B9;PD transgenic drosophila added vitamin B3:PINK1^B9+NAM[Nicotinamide（NAM）the main form of vitamin B3)].Further,observed and recorded the results about the abnormal wing postures,collapsed thorax and the motor ability（flight ability and creeping ability）;detectied the drosophila’s thorax tissue ATP generation through ATP kit,and detected the drosophila’s thorax tissue protein expression level of NDUFS3 by Western Blot,and detect the drosophila brain tissue dopamine neurons with TH staining methods.Results:Compared with the control group,Vitamin B3 treated PD transgenic drosophila decreased wings and breast abnormalities rate,improved the ability to fly and crawl ability,the abnormal of the wings rate was reduced from80.33%to 52.67%（P<0.001）,thorax tissue collapse rate decreased from13.33%to 4%（P<0.05）.The creeping height of PD model was（4.300±0.7949）cm/5s,vitamin B3 treated group,the height was（9.253±0.8920）cm/5s（P<0.001）.The relative content of ATP in thorax tissue of vitamin B3 treated group was（1.523±0.2333）mmol/L,which was 4 times more than the PD model（P<0.01）.Compared with PD group,TH positive changes on DA in the PD with vitamin B3treated group was significant（P<0.01）.Similarly NDUFS3 protein in PD was the lowest value（0.2129±0.05475）,while NDUFS3 protein increased to（0.6128±0.1622）（P<0.01）,after treatment with vitamin B3 in PD.Conclusions:Conclusion:Vitamin B3 has a protective effect on PINK1^B9,its mechanism may be related to the upregulation of NDUFS3,improving energy metabolism,so as to protect DA neurons.