| First Author | Ribeiro MC | Year | 2022 |
| Journal | Neurobiol Dis | Volume | 165 |
| Pages | 105636 | PubMed ID | 35091041 |
| Mgi Jnum | J:323678 | Mgi Id | MGI:6887294 |
| Doi | 10.1016/j.nbd.2022.105636 | Citation | Ribeiro MC, et al. (2022) Vitamin D modulates cortical transcriptome and behavioral phenotypes in an Mecp2 heterozygous Rett syndrome mouse model. Neurobiol Dis 165:105636 |
| abstractText | Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the transcriptional regulator MECP2. Mecp2 loss-of-function leads to the disruption of many cellular pathways, including aberrant activation of the NF-kappaB pathway. Genetically attenuating the NF-kappaB pathway in Mecp2-null mice ameliorates hallmark phenotypes of RTT, including reduced dendritic complexity, raising the question of whether NF-kappaB pathway inhibitors could provide a therapeutic avenue for RTT. Vitamin D is a known inhibitor of NF-kappaB signaling; further, vitamin D deficiency is prevalent in RTT patients and male Mecp2-null mice. We previously demonstrated that vitamin D rescues the aberrant NF-kappaB activity and reduced neurite outgrowth of Mecp2-knockdown cortical neurons in vitro, and that dietary vitamin D supplementation rescues decreased dendritic complexity and soma size of neocortical projection neurons in both male hemizygous Mecp2-null and female heterozygous mice in vivo. Here, we have identified over 200 genes whose dysregulated expression in the Mecp2+/- cortex is modulated by dietary vitamin D. Genes normalized with vitamin D supplementation are involved in dendritic complexity, synapses, and neuronal projections, suggesting that the rescue of their expression could underpin the rescue of neuronal morphology. Further, there is a disruption in the homeostasis of the vitamin D synthesis pathway in Mecp2+/- mice, and motor and anxiety-like behavioral phenotypes in Mecp2+/- mice correlate with circulating vitamin D levels. Thus, our data indicate that vitamin D modulates RTT pathology and its supplementation could provide a simple and cost-effective partial therapeutic for RTT. |
