Jonathan Brouillette, Ph.D.

For the past ten years, my primary research focus has consisted of studying the molecular and cellular phenomena related to memory decline during aging and in Alzheimer’s disease (AD). During my Ph.D. under the direction of Prof. Rémi Quirion at the Douglas Mental Health University Institute (McGill University), I used microarray and AAV vectors infused into the brain to identify various genes involved in memory processes that were altered during aging in a scopolamine-injected rat model as well as in memory impaired and unimpaired aged rats following analysis in the Morris water. At the end of my thesis, I initiated a project which leads to the identification of the Quinone Reductase 2 in aged memory deficits in collaboration with the pharmaceutical company Servier.

Subsequently I began my post-doctoral research in Dr. Luc Buée’s laboratory (France, Lille) in collaboration with the laboratory of Bart De Strooper (Belgium, Leuven) to study the interaction between toxic amyloid-β (Aβ) oligomers and tau in the induction of Alzheimer’s phenotype. This project was undertaken as part of the European MEMOSAD consortium (Memory loss in Alzheimer disease) involving several other laboratories across Europe. I developed a novel animal model to study the neurodegenerative effects of Aβ oligomers in vivo. This model allowed a new field of investigation since the neurotoxic effect of Aβ oligomers were mainly study so far in cell cultures or brain slices. This approach can now be used in preclinical studies of molecules that could potentially prevent neurodegeneration observed in AD. During my post-doctoral research I also studied the effects of anesthesia (Sevoflurane and cocktail of ketamine and xylaxine) on Tau pathology.

As of November 2011, I am a post-doctorate associate at Yale University in Prof. Paul Lombroso’s laboratory to study the effect of STEP phosphatase on the glutamatergic system during aging, in collaboration with Rémi Quirion (McGill University) and Pierrette Gaudreau (University of Montreal). Many studies have shown that NR2B receptors are essential for synaptic plasticity and that age-related memory deficits are associated with functional alteration of these receptors. Our results indicate that disruption of STEP activity constitutes a novel molecular mechanism to explain cognitive deficiencies that occur during aging. I also have another project investigating STEP’s role in the antidepressant action of ketamine.