Dr. Michael Zigmond

Professor, Neurology
Ph.D. University of Chicago (1968)

Office: 7016 Biomedical Science Tower 3
Telephone:412-624-4258
Fax:412-624-7327
E-mail: zigmond@pitt.edu

Cell death and neuroprotection in aging and neurodegenerative disease.


Research Summary:

Michael Zigmond and his research group are interested in neuronal cell death, survival, and adaptation, with particular attention paid to aging-related disfunction, including neurodegenerative diseases such as Parkinson's disease. Much of the current work focuses on three questions: First, what are the behavioral deficits that often occur during 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, what underlies the loss of dopamine neurons in Parkinson's disease and how do 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. Third, in what ways does stress reduce (“preconditioning”) or increase the vulnerability of brain to subsequent insults. Studies involve cell lines, primary neuronal cultures of neurons, and transgenic rodent models. The lab makes use of cell and molecular biology, histochemistry, small animal surgery, 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, and clinical neurology. Zigmond and his labmates believe that these studies will provide basic information in cellular and molecular neurobiology, as well as insights into aspects of several clinical conditions.


Links:

CNUP

Department of Neurology


Selected Publications:

  • Lindgren N, Leak RK, Carlson KM, Smith AD, Zigmond MJ. Activation of the extracellular signal-regulated kinases 1 and 2 by glial cell line-derived neurotrophic factor and its relation to neuroprotection in a mouse model of Parkinson's disease. J Neurosci Res, 86: 2039-2049, 2008.
  • Pienaar IS, Kellaway LA, Russell VA, Smith AD, Stein DJ, Zigmond MJ, Daniels WMU. Maternal separation exaggerates the toxic effects of 6-hydroxydopamine in rats: Implications for neurodegenerative disorders. Stress, 11:448-56, 2008.
  • Leak RK, Zigmond MJ, Liou AKF. Adaptation to chronic MG132 reduces oxidative toxicity by a CuZnSOD-dependent mechanism. J Neurochem, 106: 860-874, 2008.
  • Liou AKF, Leak RK, Li L, Zigmond MJ. Wild-type LRRK2 but not its mutant attenuates stress-induced cell death via ERK pathway. Neurobiology of Disease, 32116-124, 2008.
  • Daniels WM, Fairbairn LR, van Tilburg G, McEvoy CR, Zigmond MJ, Russell VA, Stein DJ. Maternal separation alters nerve growth factor and corticosterone levels but not the DNA methylation status of the exon 1(7) glucocorticoid receptor promoter region. Metab Brain Dis.;24: 615-27. 2009
  • El Ayadi A, Liou AK, Zigmond, MJ, Low concentrations of methamphetamine can protect dopaminergic cells against oxidative stress. Submitted to J. Neurosci. Res. (in revision)
  • Leak RK, Castro SL, Jaumotte JD, Smith, AD, Zigmond MJ. Assaying multiple biochemical variables from the same tissue sample. J Neuroscience Methods. 191:234-8, 2010.
  • Cohen AD, Zigmond MJ, Smith AD. Effects of intrastriatal GDNF on the response of dopamine neurons to 6-hydroxydopamine: Time course of protection and neurorestoration. Brain Res, 1370:80-8, 2011.
  • Allen E, Carlson KM, Zigmond MJ, Cavanaugh JE. L-DOPA reverses motor deficits associates with normal aging in mice. Neurosci Lett. 489:1-4, 2011.