Bone marrow-derived microglia contribute to the neuroinflammatory response and express iNOS in the MPTP mouse model of Parkinson's disease

Abstract

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication in mice results in dopamine neuron degeneration that is alleviated by prevention of microglia cell activation and blockade of iNOS production. However, the role of peripherally derived microglia in this response has not been well characterized. In the present study, we investigated the time course of infiltration and phenotypic differentiation of bone marrow-derived cells (BMDCs) following MPTP treatment in mice, using green fluorescent protein (GFP) bone marrow chimeras. BMDCs were found in the meninges, choroid plexus, blood vessels, and brain parenchyma in both saline and MPTP-treated mice. MPTP stimulated a transient, two-fold increase in the rate of BMDC infiltration into the brain, concomitant with the onset of microglia activation. The majority of BMDCs were microglial in phenotype, as assessed by morphology and expression of the pan-hematopoietic marker CD45 and the microglia marker CD11b. We did not observe BMDCs that expressed neuronal or astroglial markers. Over 90% of bone marrow-derived microglia expressed the inducible form of nitric oxide synthase (iNOS), suggesting that peripherally derived microglia may play a deleterious role in MPTP-induced degeneration.

Keywords

• Bone marrow-derived cells
• 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine
• Microglia
• Parkinson's disease
• Neuroinflammation
• iNOS