Protective Effect Of Curcumin On MPTP Mouse Model Of Parkinson’ Disease

BackgroundParkinson’s disease(PD)is the second most common neurodegenerative disease.A large number of studies have addressed the spine loss of Medium spiny neurons(MSNs)in the Caudate putamen(CPu)in patients and animal models of Parkinson’s disease,which is consistent with the occurrence of motor dysfunction in the disease.Small G protein families,including Rac1,RhoA and Cdc42,play an important role in neuronal dendritic remodeling.In recent years,many studies have suggested that curcumin may play a protective role in the prevention and treatment of Parkinson’s disease through anti-inflammation,anti-oxidation and anti-apoptosis.It has been proved that curcumin plays a preventive and therapeutic role by regulating the activity of small G protein Racl in some disease,such as liver injury and lung cancer.However,it has not been reported whether curcumin plays a protective role through the small G protein Rac1 signal pathway in the occurrence and development of PD.Thus,focusing on the CPu,we explore the protective effect of curcumin on PD model mice and its related mechanism.MethodsWe investigated the protective effect of curcumin on spine abnormalities and behavioral deficits in the MPTP mouse model of PD.Western blotting and GST pull-down assay were used to detect the activity of Racl in the CPu and the activity TH in the Substantia Nigra(SN)of the MPTP mouse model of PD.Then,constitutively active and dominant-negative mutant lentivirus of Racl were used to verify the role of CPu Racl activity in curcumin’s improvement of motor dysfunction and dendritic spine abnormalities in the MPTP mouse model of PD.ResultsPart Ⅰ:(1)Curcumin can improve the locomotor activity,grasping ability,motor coordination and balance ability of PD model mice.(2)Curcumin can reduce the loss of TH positive neurons in SN region and dendritic spines in CPu region of PD model mice.(3)Curcumin upregulates the expression of TH in SN and Rac1 GTPase,Total Racl and Tiaml in CPu.Part Ⅱ:(1)Activation of Racl was involved in curcumin-induced improvement of motor function in PD model mice.(2)Curcumin protects dopaminergic neurons in PD model mice by upregulating Racl signaling pathway in CPu.ConclusionThe purpose of this study was to explore the protective effect of curcumin on PD model mice and the regulation of Racl signal pathway in it.It was found that curcumin may improve the abnormality of dendritic spines and behavior in PD model mice by regulating Rac1 signal pathway.This study reveals the protective mechanism of curcumin on PD model mice from a new point of view,and provides a new idea for the treatment of PD.