I graduated from Emory University with a PhD in neuroscience in May of 2017, and shortly thereafter joined the Kaczorowski lab as a postdoctoral associate. I am employing a genetically diverse mouse model of Alzheimer's disease to investigate how genetic variability mediates the effects of a high fat diet on Alzheimer's-associated pathogenesis. In general, high fat diets increase risk and rate of decline in Alzheimer's disease, though in humans and in our mouse model, this is dependent on an individual's genetic context. I use a variety of behavioral, molecular, and computational techniques which will precisely identify which gene candidates and molecular networks are responsible for regulating this variability. Ultimately, these studies should lead to novel therapeutic targets for more personalized treatment strategies for Alzheimer's disease.
Advisor: Dr. Gary W. Miller
University of Maine
Disruption of neurotransmitter vesicle dynamics (transport, capacity, release) has been implicated in a variety of neurodegenerative and neuropsychiatric conditions. Here, we report a novel mouse model of enhanced vesicular function via bacterial artificial chromosome (BAC)-mediated overexpression of the vesicular monoamine transporter 2 (VMAT2; Slc18a2). A twofold increase in vesicular transport enhances the vesicular capacity for dopamine (56%), dopamine vesicle volume (33%), and basal tissue dopamine levels (21%) in the mouse striatum. The elevated vesicular capacity leads to an increase in stimulated dopamine release (84%) and extracellular dopamine levels (44%). VMAT2-overexpressing mice show improved outcomes on anxiety and depressive-like behaviors and increased basal locomotor activity (41%). Finally, these mice exhibit significant protection from neurotoxic insult by the dopaminergic toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as measured by reduced dopamine terminal damage and substantia nigra pars compacta cell loss. The increased release of dopamine and neuroprotection from MPTP toxicity in the VMAT2-overexpressing mice suggest that interventions aimed at enhancing vesicular capacity may be of therapeutic benefit in Parkinson disease.
The Alzheimer’s Association has awarded a three-year research fellowship to Amy Dunn, Ph.D., a postdoctoral associate in the Kaczorowski lab, for her studies of how genetics and diet interact to determine risk for Alzheimer’s disease.