{"doi":"10.1523/eneuro.0167-20.2020","title":"Vitamin D Supplementation Rescues Aberrant NF-κB Pathway Activation and Partially Ameliorates Rett Syndrome Phenotypes in<i>Mecp2</i>Mutant Mice","abstract":"Abstract Rett syndrome (RTT) is a severe, progressive X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulator MECP2 . We previously identified aberrant NF-κB pathway upregulation in brains of Mecp2 -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 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-κB 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-κB pathway inhibition might be a therapeutic target for RTT.","journal":"eNeuro","year":2020,"id":101498,"datarank":0.49983067652628066,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.0,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9479,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":497023,"name":"Seth M. Moore","orcid":"0000-0001-9488-3905","position":1,"is_corresponding":false},{"id":498242,"name":"Noriyuki Kishi","orcid":null,"position":2,"is_corresponding":false},{"id":481647,"name":"Jeffrey D. Macklis","orcid":"0000-0003-3662-9698","position":3,"is_corresponding":false},{"id":328987,"name":"Jessica L. MacDonald","orcid":"0000-0002-9111-5756","position":4,"is_corresponding":false},{"id":328986,"name":"Mayara C. Ribeiro","orcid":"0000-0002-0849-6771","position":0,"is_corresponding":true}],"reference_count":100,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:40:22.678835Z","pmid":"32393583","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}