| First Author | Ribeiro MC | Year | 2020 |
| Journal | eNeuro | Volume | 7 |
| Issue | 3 | PubMed ID | 32393583 |
| Mgi Jnum | J:289443 | Mgi Id | MGI:6430875 |
| Doi | 10.1523/ENEURO.0167-20.2020 | Citation | Ribeiro MC, et al. (2020) Vitamin D Supplementation Rescues Aberrant NF-kappaB Pathway Activation and Partially Ameliorates Rett Syndrome Phenotypes in Mecp2 Mutant Mice. eNeuro 7(3):ENEURO.0167-20.2020 |
| abstractText | Rett syndrome (RTT) is a severe, progressive X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulator MECP2 We previously identified aberrant NF-kappaB pathway upregulation in brains of Mecp2-null mice and demonstrated that genetically attenuating NF-kappaB rescues some characteristic neuronal RTT phenotypes. These results raised the intriguing question of whether NF-kappaB pathway inhibitors might provide a therapeutic avenue in RTT. Here, we investigate whether the known NF-kappaB pathway inhibitor vitamin D ameliorates neuronal phenotypes in Mecp2-mutant mice. Vitamin D deficiency is prevalent among RTT patients, and we find that Mecp2-null mice similarly have significantly reduced 25(OH)D serum levels compared with wild-type littermates. We identify that vitamin D rescues aberrant NF-kappaB pathway activation and reduced neurite outgrowth of Mecp2 knock-down cortical neurons in vitro Further, dietary supplementation with vitamin D in early symptomatic male Mecp2 hemizygous null and female Mecp2 heterozygous mice ameliorates reduced neocortical dendritic morphology and soma size phenotypes and modestly improves reduced lifespan of Mecp2-nulls. These results elucidate fundamental neurobiology of RTT and provide foundation that NF-kappaB pathway inhibition might be a therapeutic target for RTT. |
