Currently, Dr. Mount’s laboratory investigates early changes in brain chemistry associated with the onset of neurodegenerative disease phenotypes in murine models of neurodegenerative disease. They use a variety of behavioural tests to ascertain the timing and likely loci of a developing impairment. They then use instantaneous heat inactivation of the brain, so as to preserve the in vivo state of labile signalling intermediates for measurement with HPLC-electrochemical, HPLC-UV and conventional protein detection methods. In this manner, they have succeeded in linking early changes in behavior to presynaptic degeneration, regionaly alterations in mitochondrial electron transport chain output and to altered neurotrophic factor and cytokine expression during critical early stages of the degenerative process. This approach has revealed robust and relevant markers of disease progression and has recently revealed multiple lines of evidence for a therapeutic utility of alpha2-adrenoceptor antagonism in the TgCRND8 model of Alzheimer’s disease.
Subject Area Themes: Alzheimer's disease, ataxia, cell death, cerebellum, energy, memory, neurodegeneration, neurotrophic factors, sensorimotor function, Ataxia-telangiectasia, Parkinsons disease, energy, metabolism, mitochondria, neurodegeneration, memory, transgenic mouse, behaviour, HPLC, cell culture
Department of Psychiatry; Department of Physiology; Institute of Medical Science, University of Toronto
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