{"doi":"10.17615/ftym-4r69","title":"Insulin-like growth factor-I ameliorates demyelination induced by tumor necrosis factor-α in transgenic mice","abstract":"Our laboratories have reported that TNF-α causes myelin damage and apoptosis of oligodendrocytes and their precursors in vitro and in vivo. We also have reported that IGF-I can protect cultured oligodendrocytes and their precursors from TNF-α-induced damage. In this study, we investigated whether IGF-I can protect oligodendrocytes and myelination from TNF-α-induced damage in vivo by cross-breeding TNF-α transgenic (Tg) mice with IGF-I Tg mice that overexpress IGF-I exclusively in brain. At 8 weeks of age, compared to wildtype (WT) mice, the brain weights of TNF-α Tg mice were decreased by ~20%, while those of IGF-I Tg mice were increased by ~20%. The brain weights of mice that carry both TNF-α and IGF-I transgenes (TNF-α/IGF-I Tg mice) did not differ from WT mice. As judged by histochemical staining and immunostaining, myelin content in the cerebellum of TNF-α/IGF-I Tg mice was similar to that in WT mice and much more than that in TNF-α Tg mice. Consistently, western immunoblot analysis showed that myelin basic protein abundance in the cerebellum of TNF-α/IGF-I Tg mice was double that in TNF-α Tg mice. Compared to WT mice, the number of oligodendrocytes was decreased by ~36% in TNF-α Tg mice, while it was increased in IGF-I Tg mice by ~40%. Oligodendrocyte number in TNF-α/IGF-I Tg mice was almost as twice many as that in TNF-α Tg mice. Furthermore, IGF-I overexpression significantly reduced TNF-α-induced increases in apoptotic cell number, active caspase-3 abundance and degraded MBP. Our results indicate that IGF-I is capable of protecting myelin and oligodendrocytes from TNF-α-induced damage in vivo.","journal":"UNC Libraries","year":2021,"id":230664,"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":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":837109,"name":"George Kollias","orcid":"0000-0003-1867-3150","position":1,"is_corresponding":false},{"id":837461,"name":"A.Joseph D apos Ercole","orcid":null,"position":2,"is_corresponding":false},{"id":523416,"name":"Ping Ye","orcid":"0000-0002-5591-6812","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:55:09.211909Z","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":[]}