n/a
Article Publish Status: FREE
Abstract Title:

Vitamin D supplementation rescues aberrant NF-κB pathway activation and partially ameliorates Rett syndrome phenotypes inmutant mice.

Abstract Source:

eNeuro. 2020 May 11. Epub 2020 May 11. PMID: 32393583

Abstract Author(s):

Mayara C Ribeiro, Seth M Moore, Noriyuki Kishi, Jeffrey D Macklis, Jessica L MacDonald

Article Affiliation:

Mayara C Ribeiro

Abstract:

Rett syndrome (RTT) is a severe, progressive X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulatorWe previously identified aberrant NF-κB pathway up-regulation in brains of-null mice and demonstrated that genetically attenuating NF-κB rescues some characteristic neuronal RTT phenotypes. These results raised the intriguing question of whether NF-κB pathway inhibitors might provide a therapeutic avenue in RTT. Here, we investigate whether the known NF-κB pathway inhibitor vitamin D ameliorates neuronal phenotypes in-mutant mice. Vitamin D deficiency is prevalent among RTT patients, and we find that-null mice similarly have significantly reduced 25(OH)D serum levels compared to wildtype littermates. We identify that vitamin D rescues aberrant NF-κB pathway activation and reduced neurite outgrowth ofknockdown cortical neuronsFurther, dietary supplementation with vitamin D in early symptomatic malehemizygous null and femaleheterozygous mice ameliorates reduced neocortical dendritic morphology and soma size phenotypes, and modestly improves reduced lifespan of-nulls. These results elucidate fundamental neurobiology of RTT and provide foundation that NF-κB pathway inhibition might be a therapeutic target for RTT.There is currently no effective treatment for Rett syndrome (RTT); however, selectively re-expressingin adult mice has shown that RTT symptoms can be partially reversed, suggesting that restoration of homeostasis of downstream targets of MeCP2 could also reverse or alleviate RTT symptoms. One such potential target is the NF-κB pathway, which is aberrantly up-regulated in the brain of-mutant mice. Genetically reducing NF-κB signaling in these mice improves neuronal phenotypes. Here, we identify that the known NF-κB inhibitor vitamin D reduces the aberrant NF-κB signaling inknockdown neurons, and partially ameliorates neuronal size and complexity phenotypes in both male and female-mutant mice. Thus, this simple, cost-effective dietary supplement could contribute toward a partial therapeutic avenue in RTT.

Study Type : Animal Study

Print Options


Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2020 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.