{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:05:35Z","timestamp":1792789535741,"version":"4.5.0"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministery for University and Research, Italy","award":["\u201cFinanziamento delle attivit\u00e0 base di ricerca 2017\u201d"],"award-info":[{"award-number":["\u201cFinanziamento delle attivit\u00e0 base di ricerca 2017\u201d"]}]},{"name":"University of Campania","award":["VALERE project"],"award-info":[{"award-number":["VALERE project"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The bioactive form of vitamin D, 1,25-dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2-3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive\u2014activated and proliferative\u2014phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased \u03b2-galactosidase (B-gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator-activated-receptor-alpha (PPAR-\u03b1), reduced most of these effects. Morphological analysis of ex-vivo microglia obtained from vitamin-D-deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D.<\/jats:p>","DOI":"10.3390\/ijms22073604","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:13:10Z","timestamp":1617149590000},"page":"3604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Vitamin D Deficiency Induces Chronic Pain and Microglial Phenotypic Changes in Mice"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5019-2130","authenticated-orcid":false,"given":"Nicola","family":"Alessio","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Belardo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9813-5955","authenticated-orcid":false,"given":"Maria Consiglia","family":"Trotta","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Paino","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Boccella","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Gargano","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorizio","family":"Pieretti","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Ricciardi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Marabese","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livio","family":"Luongo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Galderisi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabatino","family":"Maione","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Guida","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jchemneu.2004.08.006","article-title":"Distribution of the Vitamin D receptor and 1\u03b1-hydroxylase in human brain","volume":"29","author":"Eyles","year":"2005","journal-title":"J. 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