{"doi":"10.1101/2020.06.10.143941","title":"Critical role for astrocyte NAD <sup>+</sup> glycohydrolase in myelin injury and regeneration","abstract":"Abstract Western-style diets cause disruptions in myelinating cells and astrocytes within the mouse CNS. CD38 has increased expression in the cuprizone and EAE demyelination models and is the main NAD + depleting enzyme in CNS tissue. Altered NAD + metabolism has been linked to both high fat consumption and Multiple Sclerosis (MS). We identified increased CD38 expression in the male mouse spinal cord following chronic high fat consumption or focal lysolecithin-induced demyelinating injury as well as in reactive astrocytes within an active MS lesion. CD38-catalytically inactive mice are significantly protected from high fat-induced NAD + depletion, oligodendrocyte loss, oxidative damage, and astrogliosis. 78c, a CD38 inhibitor, increased NAD + and attenuated neuroinflammatory changes in astrocytes induced by saturated fat. Conditioned media from saturated fat-treated astrocytes impaired oligodendrocyte differentiation pointing to indirect mechanisms of oligodendrogliopathy. Combined saturated fat and lysolecithin demyelination in cerebellar slices resulted in additional deficits in myelin proteins that were mitigated by concomitant 78c treatment. Importantly, oral 78c increased counts of oligodendrocytes and remyelinated axons after focal demyelination. Our findings suggest high fat diet impairs oligodendrocyte survival and differentiation through astrocyte-linked mechanisms mediated by the NAD + ase CD38, and highlight the use of CD38 inhibitors as potential therapeutic candidates to improve myelin regeneration.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":131894,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"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":587384,"name":"Chan‐Il Choi","orcid":null,"position":1,"is_corresponding":false},{"id":586754,"name":"Thais Peclat","orcid":"0000-0002-8907-5548","position":2,"is_corresponding":false},{"id":586755,"name":"Yong Guo","orcid":"0009-0003-4462-750X","position":3,"is_corresponding":false},{"id":505664,"name":"Whitney L. Simon","orcid":null,"position":4,"is_corresponding":false},{"id":505660,"name":"Hyesook Yoon","orcid":null,"position":5,"is_corresponding":false},{"id":505662,"name":"Laurel S. Kleppe","orcid":null,"position":6,"is_corresponding":false},{"id":231257,"name":"Claudia F. Lucchinetti","orcid":"0000-0001-5070-1196","position":7,"is_corresponding":false},{"id":115405,"name":"Claudia C.S. Chini","orcid":null,"position":8,"is_corresponding":false},{"id":256584,"name":"Eduardo N. Chini","orcid":"0000-0003-1555-4834","position":9,"is_corresponding":false},{"id":504825,"name":"Isobel A. Scarisbrick","orcid":"0000-0003-2395-589X","position":10,"is_corresponding":false},{"id":273475,"name":"Monica R. Langley","orcid":"0000-0002-3146-1067","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:16:07.542484Z","pmid":null,"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":[]}