Vitamin D Treatment Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in an Animal Model of Parkinson’s Disease, Shifting M1 to M2 Microglia Responses

Microglia-mediated neuroinflammation has been described as a common hallmark of parkinson’s disease (pd) and is believed to further exacerbate the progressive degeneration of dopaminergic neurons. current therapies are unable to prevent the disease progression. a significant association has been demonstrated between pd and low levels of vitamin d in patients serum, and vitamin d supplement appears to have a beneficial clinical effect. herein, we investigated whether vitamin d administered orally in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp)-induced preclinical animal model of pd protects against glia-mediated inflammation and nigrostriatal neurodegeneration. vitamin d significantly attenuated the mptp-induced loss of tyrosine hydrlase (th)-positive neuronal cells, microglial cell activation (iba1-immunoreactive), inducible nitric oxide synthase (inos) and tlr-4 expression, typical hallmarks of the pro-inflammatory (m1) activation of microglia. additionally, vitamin d was able to decrease pro-inflammatory cytokines mrna expression in distinct brain areas of the mptp mouse. importantly, we also assessed the anti-inflammatory property of vitamin d in the mptp mouse, in which it upregulated the anti-inflammatory cytokines (il-10, il-4 and tgf-β) mrna expression as well as increasing the expression of cd163, cd206 and cd204, typical hallmarks of alternative activation of microglia for anti-inflammatory signalling (m2). collectively, these results demonstrate that vitamin d exhibits substantial neuroprotective effects in this pd animal model, by attenuating pro-inflammatory and up-regulating anti-inflammatory processes.