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

被引:0
作者
Rosa Calvello
Antonia Cianciulli
Giuseppe Nicolardi
Francesco De Nuccio
Laura Giannotti
Rosaria Salvatore
Chiara Porro
Teresa Trotta
Maria Antonietta Panaro
Dario Domenico Lofrumento
机构
[1] University of Bari,Department of Biosciences, Biotechnologies and Biopharmaceutics
[2] University of Salento,Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy
[3] University of Foggia,Department of Clinical and Experimental Medicine
来源
Journal of Neuroimmune Pharmacology | 2017年 / 12卷
关键词
Vitamin D; Microglia; MPTP; Parkinson’s disease; Neuroinflammation;
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学科分类号
摘要
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.
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页码:327 / 339
页数:12
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