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- W4296164563 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 (SCA684Q/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." @default.
- W4296164563 created "2022-09-18" @default.
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- W4296164563 date "2022-09-16" @default.
- W4296164563 modified "2023-10-14" @default.
- W4296164563 title "Activation of TrkB-Akt signaling rescues deficits in a mouse model of SCA6" @default.
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- W4296164563 doi "https://doi.org/10.1126/sciadv.abh3260" @default.
- W4296164563 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36112675" @default.
- W4296164563 hasPublicationYear "2022" @default.
- W4296164563 type Work @default.