Howard Mount began his training at the University of Toronto as an environmental scientist. Master’s thesis work in behavioural toxicology, as well as experiences developing a federal report on pyrethroid insecticides for the National Research Council Environmental Secretariat (Ottawa) and investigating drug-induced sensitization (University of Utrecht) led him to an abiding interest in the neurochemistry of behavior and particularly to the involvement of monoaminergic systems. His doctoral thesis work was in the laboratories of Drs. Rémi Quirion and Patrica Boksa (McGill University). It explored the regulation of cellular dopamine release by excitatory amino acids.
With postdoctoral fellowship support from the Medical Research Council of Canada (MRCC) and the Fonds de la Recherche en Santé du Québec, he joined the laboratories of Drs. Cheryl Dreyfus and Ira Black at Robert Wood Johnson Medical School (UMDNJ), where he published on novel cell survival-promoting interactions between transmitter receptors and neurotrophic factors and also on the signalling states of proteins anchored within the post-synaptic density. Of particular significance was his discovery that excitatory transmitters activate metabotropic receptors on cerebellar neurons, so as to “turn-on” a p75NTR-mediated survival response to NGF. The discovery led him to postulate that p75NTR might be turned on to rescue Purkinje cells that are massively depleted in the neurodegenerative disorder, ataxia-telangiectasia. This research launched his career as an independent investigator, attracting grant and scholarship support from the AT Children’s Project, the MRCC, the CIHR New Investigator Award program, the 2000 Basil O’Connor Starter Research Scholar Award (March of Dimes, NY) and the Ontario Premier’s Research Excellence Award.
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, regionallyalterations 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.