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

• DOI: 10.1007/s11481-016-9720-7
• Publication Date: 2016-12-17T01:36:21Z
• Authors: Rosa Calvello; Antonia Cianciulli; Giuseppe Nicolardi; Francesco De Nuccio; Laura Giannotti; Rosaria Salvatore; Chiara Porro; Teresa Trotta; Maria Antonietta ...; Dario Domenico Lo...
• Keywords: Male; 0303 health sciences; Dopaminergic Neurons; MPTP Poisoning; 3. Good health; MPTP; Microglia; Neuroinflammation; Parkinson’s disease; Vitamin D; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Treatment Outcome; Neuroinflammation; Parkinson’s disease; Animals; Microglia; Vitamin D; MPTP

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.