title: Severity of experimental autoimmune encephalomyelitis is unexpectedly reduced in mice born to vitamin D-deficient mothers.
abstract: Accumulating data indicate that vitamin D, a sun-induced hormone, plays a key role in multiple sclerosis (MS) etiology. Notably, it has been shown that there is a remarkable season of birth effect in MS. We surmised that gestational vitamin D deficiency is a risk factor for MS. To test this hypothesis, a vitamin D deficiency was induced in C57BL/6 female mice 6 weeks prior to conception and prolonged until offspring birth. Contrary to our prediction, we show here that adult offspring exposed to developmental vitamin D deficiency (DVD) developed a striking milder and delayed experimental autoimmune encephalomyelitis (EAE), when compared to control offspring. Using reverse transcription and quantitative real-time PCR, we measured the expression level of 22 candidate transcripts in the spleen, the cerebrum and the spinal cord, at Day0 and Day30 post-immunization. We report here that, at Day30 post-immunization, TNF, osteopontin, H2-Eb were over-expressed and IFN was under-expressed in the spinal cord of control mice and not in DVD mice. Another discrepancy between nervous and immune systems was observed: expression of IL4 was dysregulated exclusively in the spleen. Reduced symptom severity in DVD mice can partially be explained by a nervous system-restricted over-expression of vitamin D receptor (VDR), two heat shock proteins (HSP90, HSPa8) and FK506 binding protein 1a (FKBP1a), at Day0. Our clinical test and molecular findings converge to indicate that maternal hypovitaminosis D imprints the foetus and alters the susceptibility of the offspring to EAE. We propose a new hypothesis to explain our unexpected observations.
authors.affiliation: NICN, CNRS UMR 6184, Faculté de Médecine, Université Aix-Marseille, Marseille, France.
authors.forename: Diana Andrea
authors.initials: DA
authors.lastname: Fernandes de Abreu
authors.forename: El Chérif
authors.initials: EC
authors.lastname: Ibrahim
authors.forename: José
authors.initials: J
authors.lastname: Boucraut
authors.forename: Michel
authors.initials: M
authors.lastname: Khrestchatisky
authors.forename: François
authors.initials: F
authors.lastname: Féron
mesh_terms: D000818:Animals; D017931:DNA Primers / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D050883:HSC70 Heat-Shock Proteins / Q000096:biosynthesis; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000378:metabolism; D007249:Inflammation; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D018167:Receptors, Calcitriol / Q000096:biosynthesis; D022021:Tacrolimus Binding Proteins / Q000096:biosynthesis; D014808:Vitamin D Deficiency / Q000151:congenital / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D050883:HSC70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494372:Hspa8 protein, mouse; D018167:Receptors, Calcitriol; D022021:Tacrolimus Binding Proteins