ERK/MAP Kinase activation is evident in activated microglia of the striatum and substantia nigra in an acute and chronically-induced mouse model of Parkinson's Disease.

BACKGROUND: Parkinson disease (PD) is one of the most debilitating disorder of the elderly where dopaminergic neurons of the midbrain especially in the substantia nigra (SNc) are damaged. Dopaminergic neurons are synthesized in the midbrain project to the striatum (Caudate-putamen-CPU). Few evidence have suggested that the extracellular signal-regulated kinase ½ (ERK ½) in the brain is activated after 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure, to our knowledge no study has yet been done to demonstrate whether such activation occurs in neurons or in glia.

METHODS: In the current study, we utilized both an acute and chronic model of PD using the neurotoxicant MPTP as the causative agent. Both single and double immunolabeling method as Western Blot methods were employed.

RESULTS: Immunohistochemical studies using anti-phospho-ERK ½ antibodies suggested that ERK ½ activation takes place in the striatum (CPU) and SNc of both animal models. Moreover, double immunolabeling studies using phosphor-ERK ½ and the microglial marker, CD11b or the astrocyte marker, glial fibrillary acidic protein (GFAP), suggested that the phospho ERK ½ was present exclusively in the microglia and not in the astrocytes. Western-blot results suggested that there were no alterations in ERK in either MPTP-treated animals or in control animals; however, phospho ERK ½ was found to be significantly increased in the striatum and SNc in both acute chronic mouse PD models. Tyrosine hydroxylase (TH) immunolabeling revealed significant decreases in dopaminergic neurons in the SNc in both animal models' concomitant with activation of microglia and ERK activation.

CONCLUSION: These observations suggest that ERK activation takes place following MPTP treatment and that activation of ERK occurs primarily in the microglia. The data provided also suggest that ERK activation may be involved in transcriptional activation of microglia following neurotoxicant insults.