{"doi":"10.1126/sciadv.abh3260","title":"Activation of TrkB-Akt signaling rescues deficits in a mouse model of SCA6","abstract":"Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease resulting in motor coordination deficits and cerebellar pathology. Expression of brain-derived neurotrophic factor (BDNF) is reduced in postmortem tissue from SCA6 patients. Here, we show that levels of cerebellar BDNF and its receptor, tropomyosin receptor kinase B (TrkB), are reduced at an early disease stage in a mouse model of SCA6 (SCA6 84Q/84Q ). One month of exercise elevated cerebellar BDNF expression and improved ataxia and cerebellar Purkinje cell firing rate deficits. A TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), likewise improved motor coordination and Purkinje cell firing rate and elevated downstream Akt signaling. Prolonged 7,8-DHF administration persistently improved ataxia when treatment commenced near disease onset but was ineffective when treatment was started late. These data suggest that 7,8-DHF, which is orally bioavailable and crosses the blood-brain barrier, is a promising therapeutic for SCA6 and argue for the importance of early intervention for SCA6.","journal":"Science Advances","year":2022,"id":244068,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":877202,"name":"Sriram Jayabal","orcid":"0000-0002-0485-6725","position":1,"is_corresponding":false},{"id":877891,"name":"Jacky Sheng","orcid":null,"position":2,"is_corresponding":false},{"id":877203,"name":"Eviatar Fields","orcid":"0000-0003-2469-4644","position":3,"is_corresponding":false},{"id":877204,"name":"Tsz Chui Sophia Leung","orcid":"0000-0003-2158-4300","position":4,"is_corresponding":false},{"id":676325,"name":"Sabrina Quilez","orcid":null,"position":5,"is_corresponding":false},{"id":877205,"name":"Eileen McNicholas","orcid":"0000-0002-9829-3686","position":6,"is_corresponding":false},{"id":877206,"name":"Lois Lau","orcid":"0000-0002-8576-4952","position":7,"is_corresponding":false},{"id":2210,"name":"Shixia Huang","orcid":"0000-0003-2878-4129","position":8,"is_corresponding":false},{"id":877207,"name":"Alanna J. Watt","orcid":"0000-0002-6371-6220","position":9,"is_corresponding":false},{"id":877201,"name":"Anna A. Cook","orcid":"0000-0001-7654-0212","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T00:23:25.718788Z","pmid":"36112675","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":[]}