Introduction: Parkinson’s Disease (PD) is a debilitating, age-related disorder characterized
by selective degeneration of dopaminergic neurons in the midbrain substantia nigra (SNc). Dopaminergic
neurons originating in the midbrain project to the striatum (Caudate-putamen-CPU).
Although studies 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
Material and Methods: In the current study, we utilized both an acute and a repeat dose mouse
model of PD using the neurotoxicant MPTP as the causative agent. Immunohistochemical studies
using phospho ERK ½ antibody suggested that ERK ½ activation takes place in the striatum (CPU)
and SNc of both animal models. Moreover, double immunolabeling studies using phospho 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.
Results: Western Blot results suggested that there were no alterations in ERK in either MPTPtreated
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