Friday, April 8, 3:30-4:30 p.m.
Rasmuson Hall, Room 101
Please join the Department of Biological Sciences on Friday, April 8, for the thesis defense of M.S. Biological Sciences student Pamella Conley.
Colin McGill, advisor; Jonathan Stecyk; Jason Burkhead; and Eric Murphy
Dementia is a worldwide problem that is worsening due to the increasing elderly population. The aged brain exhibits a reduced mitochondrial function, a reduced capacity to cope with redox stress, and an increased sensitization to inflammatory stimuli. Dementia is widely believed to be the result of neurodegeneration linked to neuro-inflammation. In vitro studies have shown that malate increases neuronal glutathione (GSH), inhibits activation of neutral sphingomyelinase (nSMase), and alters the neuronal sphingolipid profile associated with inflammation and apoptosis. We treated Fischer F344 rats with malate in order to determine its effect on spatial working memory in both early-onset and late-stage dementia and to evaluate its role in redox stress and bioenergetics. Working memory was significantly improved in malate-fed rats in both groups. Supplemental malate decreased indicators of redox stress and differentially altered the sphingolipid environment. Glutathione levels in the frontal cortical section of the rat brains increased with malate treatment in early onset rats while accumulation of lipid peroxides simultaneously decreased. Malate supplementation altered the sphingolipid environment of the frontal cortex in both groups; however, the effects varied significantly between early-onset and late-stage subjects. In spite of these obvious changes to the redox state of the cells, there were no significant changes in the proteomes of the frontal cortices of either age group. Our research supports that supplementation of the primary metabolite malate causes significant improvements in spatial memory and reduces markers of redox stress.