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

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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.

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Acknowledgements

We would like to thank Mrs. Mary V. Pragnell for her linguistic assistance. This study was in part supported by found from the “Dottorato di Ricerca in Morfobiologia Applicata e Citometabolismo dei Farmaci”, University of Bari, Italy; by a grant from the University of Salento, Lecce, Italy; by a grant of Foggia University (Borsa di Studio Montel 2010), Foggia, Italy.

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Authors and Affiliations

  1. Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona, 4, 70126, Bari, Italy

    Rosa Calvello, Antonia Cianciulli, Rosaria Salvatore & Maria Antonietta Panaro

  2. Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, Italy

    Giuseppe Nicolardi, Francesco De Nuccio, Laura Giannotti & Dario Domenico Lofrumento

  3. Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy

    Chiara Porro & Teresa Trotta

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  1. Rosa Calvello
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  2. Antonia Cianciulli
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  3. Giuseppe Nicolardi
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  4. Francesco De Nuccio
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  5. Laura Giannotti
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  9. Maria Antonietta Panaro
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Correspondence to Maria Antonietta Panaro.

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Rosa Calvello and Antonia Cianciulli contributed equally to this work.

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Calvello, R., Cianciulli, A., Nicolardi, G. et al. Vitamin D Treatment Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in an Animal Model of Parkinson’s Disease, Shifting M1 to M2 Microglia Responses. J Neuroimmune Pharmacol 12, 327–339 (2017). https://doi.org/10.1007/s11481-016-9720-7

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  • DOI: https://doi.org/10.1007/s11481-016-9720-7

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