PGC-1α-siRNA suppresses inflammation in substantia nigra of PD mice by inhibiting microglia.

ABSTRACT

Background and purpose: Parkinson's disease is a common degenerative disease of the central nervous system with complex pathogenesis. More and more studies have found that inflammatory response promotes the occurrence and development of the disease, in which the activation of microglia plays an important role. PGC-1α (peroxisome proliferator activated receptor-γ coactivator-1α) is the main factor in mitochondrial biogenetic, and is closely related to the inflammatory response. Our immunofluorescence test results showed that PGC-1α and microglia (Iba1) have double-labeled phenomenon. The expression of microglia in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) group increased, and PGC-1α/Iba1 double label increased. To test whether lowering the expression of PGC-1α can reduce the activation of microglia and protect the substantia nigra dopaminergic neurons, we constructed PGC-1α interference lentivirus.Methods: Immunofluorescence, western blot, and ELISA were used to detect microglial phenotype.Results: The results showed that PGC-1α interfering with lentivirus can transfect microglial cells in substantia nigra, and the PGC-1α protein level decreased in substantia nigra accordingly; TH protein expression had no statistical difference compared with MPTP group; PGC-1α interfering lentivirus reduced microglia number and activation, and at the same time the expression of iNOS and Arg1 significantly reduced compared with MPTP group. The IL-6 expression in blood detected using ELISA was significantly reduced compared with MPTP group.Conclusion: PGC-1α downregulation inhibited microglia activity, and both M1 and M2 microglial activities are reduced.