Gregory A. Ordway, Ph.D.

Ordway

Gregory A. Ordway, Ph.D. 
Professor
Department of Biomedical Sciences  

 


Contact Information:

Department of Biomedical Sciences
James H. Quillen College of Medicine
PO Box 70582
Johnson City, TN 37614-1708
Stanton-Gerber Hall (VA 178)
Room A208
423-439-8832
Fax: 423-439-2280


Key Laboratory Personnel:

Attila Szebeni, M.S.; Lab Coordinator
Katalin Szebeni, M.D.; Assistant Professor
Michelle Chandley, Ph.D.; Research Associate
Erich Lutz, Honors student


Research Interests:

My principal area of research is the study of the biological basis of clinical depression and the molecular mechanisms of antidepressant drugs. To study depression biology, we utilize brain tissue from humans who have either committed suicide or have died from accidental or natural causes, all of whom have had psychiatric diagnoses made post-mortem using a rigorous retrospective psychological examination through first-degree family members. Brain tissues are studied at the cellular and molecular level in an attempt to understand the relationship between brain biology and psychiatric illnesses that lead to suicide, particularly depressive disorders.

My laboratory has discovered specific protein and gene expression abnormalities in discrete areas of the human brain, i.e. the noradrenergic locus coeruleus and the amygdala, that are associated with severe depression. Recent findings by other laboratories have demonstrated that glia in several areas of the brain are reduced in clinical depression.  These glial findings are intriguing because glia and noradrenergic neurons have a very special and intimate relationship.  In some areas of the brain, noradrenergic neurons make contacts solely with glia and not with other neurons. Glia express receptors for norepinephrine and communicate to noradrenergic neurons via a variety of gliotransmitters, including cytokines and growth factors.  Hence, our current research is focusing on the bi-directional communication between glia and noradrenergic neurons in depression, and its modulation by antidepressant drug action.

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Using gene expression analysis, we are studying this neuron-glial communication in human postmortem brains, in animal models of depression and antidepressant drug action, and in cell culture systems.  For some of this work, we use a combination of laser capture microdissection and quantitative PCR methods. 
Laser capture microdissection/PCR allows us to study gene expression in specific types of neurons and glia (astrocytes, oligodendrocytes, microglia) captured individually from human and rodent brains.  The discovery of cell specific gene expression changes in depression, paralleled by investigations of how the expression of these specific genes are modulated by antidepressant drug treatment in animal models, has the potential to lead us to new antidepressant drug targets and novel treatment strategies for depressive disorders.


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My research is currently funded by National Institute of Mental Health (MH46692), the American Foundation for Suicide Prevention, and Sepracor, Inc.


Selected Publications:

Klimek V., Stockmeier C.A., Overholser J., Meltzer H.Y., Kalka S., Dilley G. and Ordway G.A.: Reduced levels of norepinephrine transporters in the locus coeruleus in major depression.  J. Neurosci. 17:8451-8458, 1997.

Zhu M.-Y., Blakely R.D. Apparsundaram S., and Ordway G.A.: Downregulation of the human norepinephrine transporter in intact 293-hNET cells exposed to desipramine.  J. Neurochem. 70:1547-1555, 1998.

Zhu M.-Y., Klimek V., Dilley G.E., Haycock J.W., Stockmeier C.A., Overholser J.C., Meltzer H.Y.  and Ordway G.A.:  Elevated levels of tyrosine hydroxylase in the locus coeruleus in major depression.  Biol. Psychiatry, 46:1275-1286, 1999.

Zhu M.-Y., Shamburger S., Li J. and Ordway G.A.: Regulation of the human norepinephrine transporter by cocaine and amphetamine. J. Pharmacol. Exp. Therap., 295:951-959, 2000.

Klimek V., Zhu M.-Y., Dilley G., Konick L., Overholser J., Meltzer H.Y., May W.L., Stockmeier C.A., and Ordway G.A.: Effects of long-term cigarette smoking on the human locus coeruleus.  Arch. Gen. Psychiatry., 58:821-827, 2001.

Klimek V., Schenk J.E., Han H., Stockmeier C.A. and Ordway G.A.: Dopaminergic abnormalities in amygdaloid nuclei in major depression. A postmortem study.  Biological Psychiatry 52:740-748, 2002.

Ordway G.A., Klimek V. and Mann J.J.:  Neurocircuitry of mood disorders. In: Psychopharmacology. The Fifth Generation of Progress.  (K.L. Davis, D. Charney, J.T. Coyle, C. Nemeroff, eds) Lippincott-Williams & Wilken, pp. 1051-1064, 2002.

Zhang W. and Ordway G.A. The alpha2C-adrenoceptor modulates GABA release in mouse striatum. Mol. Brain Res., 112:24-32, 2003.

Karolewicz B., Szebeni K., Stockmeier C.A., Konick L., Overholser J.C. Jurgis G., Roth B.L., and Ordway G.A.:  Low nNOS protein in the locus coeruleus in major depression.  J. Neurochem., 91:1057-1066, 2004.

Karolewicz B., Stockmeier C.A., and Ordway G.A.:  Elevated levels of the NR2C subunit of the NMDA receptor in the locus coeruleus in depression.  Neuropsychopharmacology, 30:1557-67, 2005.

Recent publications:

Karolewicz B., Szebeni K., Gilmore T., Maciag D., Stockmeier C.A. and Ordway G.A.  Elevated levels of NR2A and PSD-95 in the lateral amygdala in depression.  Int. J. Neuropsychopharmacology, 23:1-11, 2009.

Ordway G.A., Szebeni A., Duffourc M.M., Dessus-Babus S. and Szebeni K.: Gene expression analyses of neurons, astrocytes, and oligodendrocytes isolated by laser capture microdissection from human brain: Detrimental effects of laboratory humidity.  J. Neurosci. Res., 87:2430-2438, 2009.

Karolewicz B., Johnson L., Szebeni K., Stockmeier C.A., and Ordway G.A.:  Glutamate signaling proteins and tyrosine hydroxylase in the locus coeruleus of alcoholics. J. Psych. Res., 42:348-355, 2008.

Zhu M.-Y., Wang W.-P., Cai Z.-W., Regunathan S., and Ordway G.A.: Exogenous agmatine has neuroprotective effects against restraint-induced structural changes in the rat brain. Europ. J. Neurosci. 27:1320-1332, 2008.

Xiang L., Szebeni K., Szebeni A., Klimek V., Stockmeier, C.A., Karolewicz B., Kalbfleisch J. and Ordway, G.A.:  Dopamine receptor gene expression in human amygdaloid nuclei: elevated D4 receptor mRNAs in depression.  Brain Res. 1207:214-224, 2008.

Karolewicz B., Szebeni K., Gilmore T., Maciag D., Stockmeier C.A. and Ordway G.A. Elevated levels of NR2A and PSD-95 in the lateral amygdala in depression.  Int. J. Neuropsychopharmacology, 23:1-11, 2008.

Karolewicz B., Szebeni K., Gilmore T., Maciag D., Stockmeier C.A. and Ordway G.A. Elevated levels of NR2A and PSD-95 in the lateral amygdala in depression. Int. J. Neuropsychopharmacology, 23:1-11, 2009.

Ordway G.A., Szebeni A., Duffourc M.M., Dessus-Babus S. and Szebeni K.: Gene expression analyses of neurons, astrocytes, and oligodendrocytes isolated by laser capture microdissection from human brain: Detrimental effects of laboratory humidity. J. Neurosci. Res., 87:2430-2438, 2009.


Books:

Ordway, G.A., Schwartz, M. and Frazer A.:  Brain Norepinephrine: Neurobiology and Therapeutics, Cambridge University Press, 2007.


Click here for printable version

Related Links:

Computer Retrieval of Information on Scientific Projects (CRISP)  

National Institute of Mental Health

UMC Center for Psychiatric Neuroscience

American Foundation for Suicide Prevention

Allen Brain Atlas