Cell death and neuroprotection in aging and neurodegenerative disease.
Michael Zigmond and his research group are interested in neuronal cell death, survival, and adaptation with particular attention paid to aging and to neurodegenerative diseases, such as Parkinson's disease. Much of the current work focuses on two questions: First, what are the motoric and cognitive deficits that occur in normal aging, what is the underlying neuropathology, and can such the dysfunctions be abated by interventions such as trophic factors and exercise (which increases endogenous trophic factors). Second, the group is asking what underlies the loss of dopamine neurons in Parkinson's disease and how trophic factors and exercise act to decrease the vulnerability of these neurons. Particular interest is given to the role of signaling cascades (e.g., Ras/Erk, PI3K/Akt) in increasing neuronal resiliency. Studies involve cell lines, primary cultures of dopamine neurons, and transgenic rodent models. The lab makes use of cell and molecular biology, immunocytochemistry, microdialysis, and behavioral analysis. Many of these studies are part of collaborative projects, permitting an extension of the work into areas of primate models, gene expression, electrophysiology, and clinical neurology. Zigmond and his labmates believe that these studies will provide basic information on the neurobiology of synaptic transmission, as well as insights into aspects of several clinical conditions.
Cohen, A.D., Tillerson, J.L., Smith, A.D., Schallert, T. and Zigmond, M.J. Neuroprotective effects of prior limb use in 6-hydroxydopamine-treated rats: Possible role of GDNF. J. Neurochem, 85: 299-305, 2002.
Ding, Y.M., Jaumotte, J.D., Signore, A.P. and Zigmond, M.J. Effects of 6-hydroxydopamine on primary cultures of substantia nigra: Specific damage to dopamine neurons and the impact of glial cell line-derived neurotrophic factor. J. Neurochem, 89: 776-787, 2004.
Smith, A.D., Kozlowski, D.A., Bohn, M.C. and Zigmond, M.J. Effect of AdGDNF on dopaminergic neurotransmission in the striatum of 6-OHDA-treated rats. Exp. Neurol, 193: 420-426, 2005.
Cavanaugh, J.E., Jaumotte, J.D., Lakoski, J.M. and Zigmond, M.J. The role of ERK1/2 and ERK5 in dopaminergic cell survival under basal conditions and in response to oxidative stress. J Neurosci Res. 84: 1367-75, 2006
Leak, R.K., Liou, A.K.F., Zigmond, M.J. Effect of sublethal 6-hydroxydopamine on the response to subsequent oxidative stress in dopaminergic cells: evidence for preconditioning. J Neurochem. (Epub ahead of print. 2006 Sep 4.)