Michael F. Salvatore, Ph.D.
Assistant Professor
Department of Pharmacology, Toxicology and Neuroscience
Ph.D., 2000, Neuroscience, Louisiana State University Health Sciences Center-New Orleans
Postdoctoral, Dept. of Anatomy & Neurobiology, University of Kentucky

Major Research Interests:
Molecular Players in Age-related Behavioral and Motoric Dysfunction and in
Neurodegenerative Diseases

The behavioral components of aging include changes in cognitive and motor function. Parkinson’s Disease is one such disease that is associated with aging but is distinct from the cognitive and motoric deficiencies seen in aging in terms of actual disease progression, the presentation hallmark signs, and synaptic functions as seen in animal studies. Notably, while there is a major loss of dopamine in the nigrostriatal system in postmortem tissue of the Parkinson’s Disease patient, the loss of dopamine in the aged individual showing Parkinson’s signs is regionally distinct and of much less magnitude. These observations bring to bear some critical questions. 1) How are dopamine biosynthesis and its regulation different between these two neurobiologically-distinct, yet behaviorally-similar, conditions? 2) What is the role of dopamine function in the substantia nigra in motor behavior?

We note that dopamine levels between the striatum and substantia nigra are about 10-fold less in the substantia nigra than in the striatum in the normal rat. Because this disparity is based upon dopamine levels normalized to tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis, it is at first striking that such differences would exist in the same neuron. This difference in dopamine regulation could also mean that a loss of dopamine function in the substantia nigra may be more critical than a loss of similar magnitude in the striatum because there is much less dopamine in the substantia nigra at the start.

Our goal is to further study the regulation of dopamine in the nigrostriatal system, paying particular attention to critical molecular players involved in its regulation in vivo under “normal” conditions as well as that in aging and in models of neurodegeneration. Recent studies with a growth factor (GDNF) in Parkinson’s disease patients and my collaborative work suggest that restoration of dopamine function in the nigrostriatal system is critical for the restoration of motor function in the Parkinson’s patient as well as in the elderly. Identification of critical proteins involved with the regulation of neurotransmitters, like dopamine in the case of Parkinson’s disease, is critical for drug development to improve the quality of life in the elderly and in those afflicted with neurodegenerative disease.

Selected Recent Publications:
Ankenman R. and Salvatore M.F. Low dose alpha-methyl-para-tyrosine (AMPT) in the treatment of dystonia and dyskinesia. J. Neuropsych. Clin. Neurosci. in press.

Salvatore, M.F., Fisher, B., Surgener, S.P., Gerhardt, G.A., and Rouault, T. Neurochemical investigations of dopamine neuronal systems in iron-regulatory protein 2 (IRP-2) knockout mice. Brain Res. Mol. Brain Res. 139, 341-347, 2005.

Stanford, J.A., Salvatore, M.F., Joyce, B.M., Zhang, H., Gash, D.M., Gerhardt, G.A. Bilateral effects of unilateral intrastriatal GDNF on locomotor-excited and nonlocomotor-related striatal neurons in aged F344 rats. Neurobiol. Aging, EPub Nov 25 2005.

Salvatore, M.F ., Zhang, J.L., Large, D.M., Wilson, P.E., Thomas, T.D., Gash, C.R., Haycock, J.W., Stanford, J.A., Bing, G., Gash, D.M., and Gerhardt, G.A. Striatal GDNF administration increases tyrosine hydroxylase phosphorylation in the rat striatum and substantia nigra. J. Neurochem. 90(1), 245-254, 2004.

Salvatore, M.F ., Hudspeth, O., Arnold, L.E., Wilson, P.E., Stanford, J.A., Mactutus, C.F., Booze, R.M., and Gerhardt, G.A. Prenatal cocaine exposure alters potassium-evoked dopamine release dynamics in rat striatum. Neuroscience 123(2), 481-490, 2004.

Salvatore, M.F ., Apparsundaram, S., and Gerhardt, G.A. Decreased plasma membrane expression of striatal dopamine transporter in aging. Neurobiol. Aging. 24(8), 1147-1154, 2003.

Salvatore, M.F ., Waymire, J.C., and Haycock, J.W. Depolarization-stimulated catecholamine biosynthesis: Involvement of protein kinases and tyrosine hydroxylase phosphorylation sites in situ. J. Neurochem. 79(2), 349-360, 2001.

Salvatore, M.F., Garcia-Espana, A., Goldstein, M., Deutch, A.Y., and Haycock, J.W. Stoichiometry of tyrosine hydroxylase phosphorylation in the nigrostriatal and mesolimbic systems in vivo: Effects of acute haloperidol and related compounds. J. Neurochem. 75(1), 225-232, 2000.

Contact Info:
Dr. Michael F. Salvatore
Assistant Professor
Department of Pharmacology, Toxicology and Neuroscience
Louisiana State University Health Sciences Center
1501 Kings Highway
Shreveport, LA 71130-3932
318-675-7874
msalva@lsuhsc.edu