Neurobiology of stress and neurodegenerative disease

Description of projects available to graduate students:
Dr. Zigmond’s research group focuses on the brain’s response to stress and injury. Particular attention is given to neurons using the catecholamines norepinephrine and dopamine. At present our work can be divided into three major projects. First, we are examining the regulation of survival and death in dopamine neurons, with particular attention to the impact of survival factors, (e.g., GDNF) and neurotoxins (e.g., 6-hydroxydopamine). We also are examining the impact of increased synuclein gene expression on neuronal survival. (Synuclein has recently been implicated in some forms of familial Parkinson’s disease.) Second, we are studying the effects of stress on the transcription of mRNA for tyrosine hydroxylase, the rate-limiting enzyme for catecholamine biosynthesis as well as the functional consequences of those mRNA changes. Third, we are exploring the role of glutamate in triggering stress-induced dopamine synthesis and release, and looking at the long-term consequences of stress, including possible neurotoxicity. Although our work is in animal models and in tissue culture, we have a strong interest in the relationship of our work to clinical disease, particularly Parkinson’s disease, schizophrenia, and post-traumatic stress disorder.

Techniques graduate student will learn:
Our in vivo work involves small animal surgery and microdialysis, a method by which extracellular fluid can be collected from a freely moving animal. Our in vitro studies make use of primary cells, transformed cell lines, acute brain slices, and organotypic slice cultures. Cells are examined in their basal state, as a function of the contents of the culture medium (e.g., the addition of a toxin), and after transfection with specific DNAs (e.g., synuclein). Analytical techniques include HPLC, liquid scintillation spectroscopy, immunocytochemistry, and analyses of DNA, mRNA, and proteins. Rotation students are encouraged to select a question and set of methodologies of interest to them from within this general framework, to begin by working with another member of the research group, and then to branch out into an independent study.