Journal
FASEB JOURNAL
Volume 28, Issue 6, Pages 2398-2413Publisher
WILEY
DOI: 10.1096/fj.13-246546
Keywords
brain function; oxytocin; prenatal; autoimmunity; behavior; vasopressin
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Funding
- David and Annette Jorgensen Foundation
- Ames CHORI Foundation
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Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established. Here, we present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE. The proposed mechanism explains 4 major characteristics associated with autism: the low concentrations of serotonin in the brain and its elevated concentrations in tissues outside the bloodbrain barrier; the low concentrations of the vitamin D hormone precursor 25-hydroxyvitamin D [25(OH) D3]; the high male prevalence of autism; and the presence of maternal antibodies against fetal brain tissue. Two peptide hormones, oxytocin and vasopressin, are also associated with autism and genes encoding the oxytocin- neurophysin I preproprotein, the oxytocin receptor, and the arginine vasopressin receptor contain VDREs for activation. Supplementation with vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder.
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