11 research outputs found
Blood recirculation and pharmacological responsiveness of the cerebral vasculature following prolonged ischemia of cat brain.
Soy Isoflavones in Integrative Oncology: Increased Efficacy and Decreased Toxicity of Cancer Therapy
Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic
Preclinical and Potential Applications of Common Western Herbal Supplements as Complementary Treatment in Parkinson's Disease
Evaluation of radioprotective activities of Rhodiola imbricata Edgew – A high altitude plant
Protective Effects of Salidroside on Hypoxia/Reoxygenation Injury by Sodium Hydrosulfite in PC12 Cells
Short-term succinic acid treatment mitigates cerebellar mitochondrial OXPHOS dysfunction, neurodegeneration and ataxia in a Purkinje-specific spinocerebellar ataxia type 1 (SCA1) mouse model.
Mitochondrial dysfunction plays a significant role in neurodegenerative disease including ataxias and other movement disorders, particularly those marked by progressive degeneration in the cerebellum. In this study, we investigate the role of mitochondrial oxidative phosphorylation (OXPHOS) deficits in cerebellar tissue of a Purkinje cell-driven spinocerebellar ataxia type 1 (SCA1) mouse. Using RNA sequencing transcriptomics, OXPHOS complex assembly analysis and oxygen consumption assays, we report that in the presence of mutant polyglutamine-expanded ataxin-1, SCA1 mice display deficits in cerebellar OXPHOS complex I (NADH-coenzyme Q oxidoreductase). Complex I genes are upregulated at the time of symptom onset and upregulation persists into late stage disease; yet, functional assembly of complex I macromolecules are diminished and oxygen respiration through complex I is reduced. Acute treatment of postsymptomatic SCA1 mice with succinic acid, a complex II (succinate dehydrogenase) electron donor to bypass complex I dysfunction, ameliorated cerebellar OXPHOS dysfunction, reduced cerebellar pathology and improved motor behavior. Thus, exploration of mitochondrial dysfunction and its role in neurodegenerative ataxias, and warrants further investigation