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

Abstract

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.

Vitamin D protects dopaminergic neurons against neuroinflammation and oxidative stress in hemiparkinsonian rats

“…A post-mortem study showed the increased levels of TNF-α and other inflammatory mediators in the brain of Parkinson’s disease patients [76]. VD3 was shown to significantly attenuate the loss of TH-positive neuronal cells, microglial cell activation, iNOS expression, among other typical hallmarks of microglia activation, in an animal model of PD similar to ours [75]. …”

“…In the last decades, neuroinflammation has been considered an important cause for progression of PD [73, 74]. In the MPTP-induced PD model, researchers demonstrated that the treatment with VD3 attenuates iNOS and pro-inflammatory cytokines expression [75]. The same pattern could be observed in animal models using the 6-OHDA neurotoxin.…”

Targets and Mechanisms in Prevention of Parkinson's Disease through Immunomodulatory Treatments

“…Calvello et al . recently showed that administration of vitamin D to methylphenyltetrahydropyridine‐intoxicated mice, attenuated neuronal loss, microglial activation, iNOS and TLR4 expression and upregulated anti‐inflammatory cytokines IL‐10, IL‐4 and TGF‐ β .…”

“…Another group demonstrated in a mouse model of PD, that blocking NF-jB signalling improved motor deficits, alleviated neuronal necrosis, decreased the expression of pro-inflammatory cytokines IL-6 and IL-1b and antagonized microglia-induced neuroinflammation [61]. Calvello et al [62] recently showed that administration of vitamin D to methylphenyltetrahydropyridine-intoxicated mice, attenuated neuronal loss, microglial activation, iNOS and TLR4 expression and upregulated anti-inflammatory cytokines IL-10, IL-4 and TGF-b.…”

The Prevention of Alzheimer's Disease and Parkinson’s Disease by Monascus purpureus NTU 568-Fermented Compounds

“…Relevant research however, has not reached consistent conclusions, with some studies indicating that fats and fatty acids also have protective effect on neurons, and can reduce the risk of disease. Furthermore, studies have tentatively shown that estrogen and non-steroidal anti-inflammatory drugs may also have protective functions [11][12][13]. Based on the above, inhibition of oxidative stress may be an important way of alleviating and preventing PD.…”