title: 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.
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona, 4, 70126, Bari, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Calvello
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona, 4, 70126, Bari, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Cianciulli
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nicolardi
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: De Nuccio
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Giannotti
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona, 4, 70126, Bari, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Salvatore
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Porro
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Trotta
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona, 4, 70126, Bari, Italy. mariaantonietta.panaro@uniba.it.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Panaro
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, Italy.
authors.forename: Dario Domenico
authors.initials: DD
authors.lastname: Lofrumento
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016896:Treatment Outcome; D014807:Vitamin D / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014807:Vitamin D
keywords: MPTP; Microglia; Neuroinflammation; Parkinson’s disease; Vitamin D