James R. Brorson, M.D.

Primary:

Associate Professor, Department of Neurology

Secondary:

Committee on Neurobiology
Committee on Cellular and Molecular Physiology

Education:

Degree	Year	Institution	Area
AB	1981	Princeton University	Physics
MD	1985	University of Chicago
Residency	1986-1989	University of Pennsylvania	Neurology
Research Fellowship	1989-1993	University of Chicago, Departments of Neurology and Pharmacological and Physiological Sciences
Board Certified	1991	American Board of Psychiatry and Neurology	Neurology


Phone:	(773) 702-7215
E-Mail:	jbrorson@neurology.bsd.uchicago.edu
Address:	AMB S232C (MC 2030)
Web page:	http://neurology.uchicago.edu/Person.aspx?PersonID=73 http://neurobiology.bsd.uchicago.edu/faculty/brorsonneuro.htm

Research Summary

AMPA receptor molecular physiology and mechanisms of excitotoxicity in central neurons

My research aims for the discovery of mechanisms of the physiological mechanisms causing selective neuronal death in neurodegenerative diseases. We have sought to define the molecular basis for glutamate-induced excitotoxicity in central neurons, by examining glutamate receptor pharmacology and the glutamate receptor subunit expression patterns in cultured primary central neurons. An important role for AMPA receptors has been found in excitotoxic damage to cerebellar Purkinje cells and to spinal motor neurons, and we have linked this toxicity to specific features of expressed AMPA receptors in these neurons. Current experiments aim at defining the molecular patterns of subunit expression in individual neurons responsible for these important physiological differences in AMPA receptors, using patch-clamping and single-cell PCR techniques.

In cerebral ischemia and several neurodegenerative disease, nitricoxide (NO) mediates much of the damage to neurons. A second focus has aimed at defining the mechanisms by which NO is toxic to neurons. We have found that NO causes impairment of Ca2+ homeostatic mechanisms in hippocampal neurons, due in part to a severe impairment of energy metabolism. We are delineating the direct effects of toxic NO levels on neuronal mitochondrial and their relationship to subsequent necrotic or apoptotic death. Understanding these interrelated mechanisms underlying selective neuronal vulnerability may unlock secrets of the pathophysiology of neurodegenerative conditions, pointing to new therapeutic approaches.

Selected Publications

J.R. Brorson, P.A. Manzolillo, S.J. Gibbons, and R.J. Miller. AMPA receptor desensitization predicts the selective vulnerability of cerebellar Purkinje cells to excitotoxicity. Journal of Neuroscience, 15:4515-4524, 1995.

J.R. Brorson, R.A. Sulit, and H. Zhang. Nitric oxide disrupts Ca²⁺ homeostasis in hippocampal neurons. Journal of Neurochemistry, 68:95-105, 1997.

J.R. Brorson, P.T. Schumacker, and H. Zhang. Nitric oxide acutely inhibits neuronal energy production. Journal of Neuroscience, 19:147-158, 1999.

W. Vandenberghe, E.C. Ihle, D.K. Patneau, W. Robberecht and J.R. Brorson. AMPA receptor current density, not densitization, predicts selective motoneuron vulnerability. Journal of Neuroscience, 20:7158-7166, 2000.

W. Vandenberghe, W. Robberecht and J.R. Brorson. AMPA receptor calciuim permeability, gluR2 expression, and selective motoneuron vulnerability. Journal of Neuroscience, 20:123-132, 2000.

Updated 10/2/07.