Professor of Pharmacology
Ph.D., UT Health Science Center – Houston
The Barshop Institute for Longevity and Aging Studies
|• receptor mechanisms||• tyrosine hydroxylase|
|• hypertension||• depression|
|• Parkinson’s disease||• aging|
|• dopamine neurons||• Rapamycin|
My research has two major objectives: the first is directed toward understanding receptor mechanisms involved in regulating tyrosine hydroxylase (TH) gene expression, the rate limiting enzyme in the synthesis of catecholamines. The latter substances are crucially involved in various life-sustaining functions and are implicated in diseases such as hypertension, depression and Parkinson’s disease. We are examining the signal transduction mechanisms that mediate the effects of selected neurotransmitter and neuromodulators on TH gene expression in a cultured adrenal chromaffin cell line. Most recently, we have focused on vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors and glucocorticoid receptors. We have investigated both transcriptional and post-transcriptional responses to PACAP and VIP and found that the PAC1 receptor distinguishes between the two agonists by stabilizing TH mRNA in response to PACAP, but not VIP. We are investigating intracellular signaling pathways in this response. We also recently identified the glucocorticoid responsive element in the promoter region of the TH gene. We are examining how second messenger pathways that are stimulated by neuropeptide receptors modulate the transcriptional responses to glucocorticoids.
The second research objective is directed toward understanding the role of oxidative stress in the aging brain. One project is aimed at determining how reactive catecholamine metabolites contribute to neuropathology of aging and Parkinson’s disease. We are particularly interested in the role that 3,4-dihydroxyphenylacetaldehyde (DOPAL) plays in degeneration of dopamine neurons. This highly reactive metabolite of dopamine becomes elevated in Parkinson’s disease and is neurotoxic. Rotenone, a pesticide that reproduces the pathology of Parkinson’s disease in rats, has been shown to elevate DOPAL in cultured cells. DOPAL is believed to be cleared by the mitochondrial aldehyde dehydrogenase (ALDH2). We have developed an ALDH2 knockout mouse to determine the role of this enzyme in DOPAL catabolism. We are also using this new mouse model to study the role of DOPAL in the pathology of Parkinson’s disease.
- Tardif, S., Ross, C., Bergman, P., Fernandez, E., Javors, M., Salmon, A., Spross, J., Strong, R. and Richardson, A. (2014) Testing Efficacy of Administration of the Antiaging Drug Rapamycin in a Nonhuman Primate, the Common Marmoset. J Gerontol A Biol Sci Med Sci Jul 19. pii: glu101. [Epub ahead of print]
- Liu, Y., Diaz, V., Fernandez, E., Strong, R., Ye, L., Baur, JA., Lamming, DW., Richardson, A. and Salmon AB (2014) Rapamycin-induced metabolic defects are reversible in both lean and obese mice. Aging (Albany NY) Sep;6(9):742-54
- Rodriguez, KA., Dodds, SG., Strong, R., Galvan, V., Sharp, ZD. and Buffenstein, R. (2014) Divergent tissue and sex effects of rapamycin on the proteasome-chaperone network of old mice. Front Mol Neurosci Nov;7:83-83
- Strong, R., Miller, RA., Astle, CM., Baur, JA., de Cabo, R., Fernandez, E., Guo, W., Javors, M., Kirkland, JL., Nelson, JF., Sinclair, DA., Teter, B., Williams, D., Zaveri, N., Nadon, NL. and Harrison, DE. (These authors contributed equally) (2013) Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium chain triglyceride oil on lifespan of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci 68:6-16
- Strong, JR. (2013) Homozygous Deletion of Glutathione Peroxidase 1 and Aldehyde Dehydrogenase 1a1 Genes Is Not Associated with Schizophrenia-Like Behavior in Mice. J Biochem Pharmacol Res Dec;1(4):228-235