Aim 1 Elucidate mechanism underlying MitoQ rescue of motor coordination in Sacs-/- mice:
(i)test mitochondrial dynamics and morphology using Mito-tracker administered intracellularly in Purkinje cells in treated and untreated Sacs−/− mice, (ii) test mitochondrial function using assays for mitochondrial respiration and energy consumption, and (iii) determine whether MitoQ rescues the abnormal somatodendritic localization of phosphorylated neurofilament in Sacs−/− mice.In addition to understanding the mechanism by which MitoQ rescues motor behaviour, the work will continue with the Brais lab to understand how and if a drug recently identified by a drug screen they conducted with V151 improves Purkinje cell morphological and physiological deficits.
Aim 2 Identify mechanism(s) underlying Purkinje cell firing deficits in Sacs-/- mice.
Over the coming 2018/2019 year we expect to make substantial advances in understanding the following 5 questions:
(a) How does MitoQ lead to behavioral improvements in Sacs−/− mice?
(b) Does V151 rescue physiological abnormalities in Sacs−/− mice?
(c) Are glutamate transporters altered in Sacs−/− mouse cerebellum?
(d) Does rescue of firing rate directly ameliorate behavioral phenotype in Sacs−/− mice?
(e) Is zebrin neuroprotective in Sacs−/− mouse cerebellum?
Duration : One year
Dr. Alanna Watt, Department of Biology McGill University Bellini Life Sciences Bldg.
3469 Sir William Osler, Montreal, Quebec Canada H3G 0B1 Office: Rm. 265 | Lab: Rm. 257
Tel: (514)-398-2806; Fax: (514)-398-5069; Email: email@example.com
Dr. Anne McKinney, Department of Pharmacology and Therapeutics, McGill University Bellini Life Sciences Bldg
3469 Sir William Osler, Montreal, Quebec Canada H3G 0B1
Tel: (514)-398-5685; Fax: (514)-398-2045; Email: firstname.lastname@example.org