A multi-omics analysis reveals vitamin D supplementation since childhood modulates molecules for signal transductions in the mouse striatum - 21/08/24
Abstract |
Vitamin D is a critical fat-soluble vitamin for the nervous system. Research suggests a potential link between vitamin D deficiency and attention-deficit hyperactivity disorder (ADHD), particularly in children and adolescents. The core symptoms of ADHD are associated with deficits in striatal functions, and maintaining sufficient levels of vitamin D may help prevent or alleviate ADHD symptoms. However, the molecular changes in the striatum caused by vitamin D supplementation that may contribute to the brain processes linked to ADHD symptoms remain unclear. In this study, we established a mouse model fed diets with three different dose gradients of vitamin D3 (0, 500, and 2000 IU/kg·day) from postnatal day 21 (P21) to 14 weeks of age. Striatal tissues from mice with gradient vitamin D3 intake were subjected to reduced representation bisulfite sequencing (RRBS), RNA-sequencing, and neurotransmitter profiling by liquid chromatography-mass spectrometry (LC-MS). Our findings indicate that vitamin D supplementation since childhood influenced the overall landscape of DNA methylations and the expression of many genes involved in critical neurological functions in a dose-dependent manner. Additionally, our data demonstrate how vitamin D modulated neuropeptide signaling pathways, as well as cholinergic and dopaminergic synapses in the striatum, through an orchestrated mechanism involving epigenetic and transcriptional regulations. Furthermore, we observed a synergistic effect of vitamin D on dopamine release following acute methylphenidate injection into our mouse model. In summary, this study provides mechanistic insights into how dietary vitamin D supplementation since childhood can modulate specific signal transductions among striatal cells, underscoring the importance of vitamin D supplementation for ADHD management.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Establishing a mouse model by controlling daily vitamin D3 intake since childhood. |
• | Vitamin D influences striatal DNA methylations and gene expression dose-specifically. |
• | Vitamin D regulates striatal signal-transduction at DNA methylation and mRNA levels. |
• | Vitamin D has a synergistic effect on dopamine release with methylphenidate. |
Keywords : Vitamin D, Striatum, ADHD, Epigenetics, Transcriptome, Neurotransmitters
Plan
Vol 178
Article 117145- septembre 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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