1α,25-Dihydroxyvitamin D(3) Protects Dopaminergic Neurons in Rodent Models of Parkinson's Disease through Inhibition of Microglial Activation

BACKGROUND: Recent studies have demonstrated the molecular basis of the immunomodulatory and anti-inflammatory activities of 1,25-dihydroxyvitamin D(3)(1,25-(OH)(2)D(3)). This hormone improves behavioral deficits and normalizes the nigral dopamine levels in animal models of Parkinson's disease (PD). METHODS: We studied whether the administration of 1,25-(OH)(2)D(3) would protect against 6-hydroxydopa (6-OHDA)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury, and its potential regulatory effect on microglia activation. RESULTS: We found that 1,25-(OH)(2)D(3) pretreatment significantly decreased 6-OHDA- and MPTP-induced dopaminergic neuronal loss in the substantia nigra pars compacta by preventing the activation of microglia. This observed neuroprotective effect in MPTP-treated mice that were given 1,25-(OH)(2)D(3) may be attributable to inhibition of proinflammatory cytokine expression. CONCLUSION: These results suggest that 1,25-(OH)(2)D(3) is a potentially valuable neuroprotective agent; it may therefore be considered for the treatment of pathologic conditions of the central nervous system, such as PD, where inflammation-induced neurodegeneration occurs.