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Janet Dubinsky, Ph.D. Professor, Department of Neuroscience E-mail: dubin001@umn.edu

Research Interests:

Glutamate, the major excitatory neurotransmitter in the central nervous system, can be toxic when applied to neurons at high concentrations. Overstimulation of central glutamate receptors results in a slowly progressive neuronal death both in vitro and in vivo. This "excitotoxicity" is believed to contribute to both necrotic and apoptotic neurodegeneration connected with both acute and progressive neurological disorders such as trauma, stroke, epilepsy, Huntington's disease, and AIDS-related dementia. The laboratory's efforts historically have been aimed at understanding the intracellular, physiological consequences of overstimulation of glutamate receptors.

At the cellular level, we are studying intracellular ionic homeostasis and metabolic function in cultured central neurons. We employ microscope-based photometry and image processing, immunocytochemistry, biophysical and biochemical techniques on cultured neurons and isolated CNS mitochondria.  We have studied the time course of intracellular calcium and pH changes and the involvement of molecular oxygen.   We have examined the invovlement of the  mitochondrial permeability transition in isolated CNS mitochondria from normal and  Huntington's Disease model mice.  At the systems level, we are currently examining metabolite changes in brains of the Huntington's Disease model mice. 

Selected Publications:

Tkac I, Dubinsky JM, Keene CD, Gruetter R, Low WC. Neurochemical changes in Huntington R6/2 mouse striatum detected by in vivo 1H NMR spectroscopy.
J Neurochem. 2007 Mar;100(5):1397-406.

Brustovetsky N, R.LaFrance, K.J. Purl, T. Brustovetsky, C.D. Keene, W.C. Low, and J.M. Dubinsky.  2005  Age-Dependent Changes in the Calcium Sensitivity of Striatal Mitochondria in Mouse Models of Huntington's Disease.  J Neurochem. 93:1361-70.

LaFrance, R, N Brustovetsky, C Sherburne, D DeLong, JM Dubinsky, 2005 Age-Related Changes in Regional Brain Mitochondria from Fischer 344 Rats.  Aging Cell  4:139-145.

Brustovetsky T., Purl K, Young A, Shimizu K and Dubinsky JM. 2004 Dearth of Glutamate Transporters Contributes to Striatal Excitotoxicity, Exp Neurol 189:222-30.

Dubinsky JM, N Brustovetsky, R LaFrance 2004 Protective Roles of CNS Mitochondria J. Bioeng Biomemb 36:299-302.

Brustovetsky, N., Dubinsky, J.M., Antonsson, B., and Jemmerson, R. 2003 Two pathways for tBID-Induced Cytochrome c Release from Rat Brain Mitochondria: BAK- versus BAX-Dependence. J Neurochem 84:196-207.

Brustovetsky N, Brustovetsky T, Purl KJ, Capano M, Cromton M and Dubinsky JM 2003 Increased Susceptibility of Striatal Mitochondria to Calcium-Induced Permeability Transition. J. Neurosci. 23:4858-67.