My laboratory is interested in how the nervous system adapts at a molecular and cellular level to changes in the organism’s activity or environment. More specifically, we study changes in gene expression in brain and peripheral nervous system in response to stress, environmental insults that lead to nerve damage, or administration of addictive drugs of abuse.

The gene that we study codes for the enzyme tyrosine hydroxylase, which catalyzes the key step in the synthesis of catecholamines. These, in turn, are important neurotransmitters in the nervous system; when released from the adrenal medulla, they also serve as circulating hormones. One major focus of our work is the regulation of this gene in the dopamine neurons of the midbrain, which send projections to the striatum. The loss of these nigrostriatal neurons during Parkinson’s disease or after treatment with certain neurotoxins leads to crippling motor dysfunctions.

Our research is aimed at understanding the molecular mechanisms, cell signaling pathways and receptors that mediate the response of the tyrosine hydroxylase gene in these nigrostriatal neurons under normal conditions. Then we then can determine whether these mechanisms are compromised or enhanced after treatment with neurotoxins such as MPTP, paraquat or amphetamines. These studies will shed light on the intracellular mechanisms that control gene expression in the nervous system in response to environmental toxins.

Recent Publications

Nagase H, Yamakuni T, Matsuzaki K, Maruyama Y, Kasahara J, Hinohara Y, Kondo S, Mimaki Y, Sashida Y, Tank AW, Fukunaga K, Ohizumi Y. 2005. Mechanism of neurotrophic action of nobiletin in PC12D cells. Biochemistry. Oct 25;44(42):13683-13691.

Osterhout CA, Sterling CR, Chikaraishi DM, Tank AW. 2005. Induction of tyrosine hydroxylase in the locus coeruleus of transgenic mice in response to stress or nicotine treatment: lack of activation of tyrosine hydroxylase promoter activity. J Neurochem. Aug;94(3):731-741.

Sun B, Chen X, Xu L, Sterling C, Tank AW. 2004. Chronic nicotine treatment leads to induction of tyrosine hydroxylase in locus ceruleus neurons: the role of transcriptional activation. Mol Pharmacol. Oct;66(4):1011-1021

Yoshimura R, Xu L, Sun B, Tank AW. 2004. Nicotinic and muscarinic acetylcholine receptors are essential for the long-term response of tyrosine hydroxylase gene expression to chronic nicotine treatment in rat adrenal medulla. Brain Res Mol Brain Res. Jul 26;126(2):188-197.

Thiruchelvam M, McCormack A, Richfield EK, Baggs RB, Tank AW, Di Monte DA, and Cory-Slechta DA. 2003. Age-related irreversible progressive nigrostriatal dopaminergic neurotoxicity in the paraquat and maneb model of the Parkinson's disease phenotype. Eur J Neurosci. Aug;18(3):589-600.

Sun B, and Tank AW. 2003. c-Fos is essential for the response of the tyrosine hydroxylase gene to depolarization or phorbol ester. J Neurochem. Jun;85(6):1421-1430.

Sun B, Sterling CR, Tank AW. 2003. Chronic nicotine treatment leads to sustained stimulation of tyrosine hydroxylase gene transcription rate in rat adrenal medulla. J Pharmacol Exp Ther. Feb;304(2):575-588.

Sun B and Tank AW. 2002. Overexpression of c-Fos is sufficient to stimulate tyrosine hydroxylase (TH) gene transcription in rat pheochromocytoma PC18 cells. J Neurochem. Jan;80(2):295-306.

Piech-Dumas KM, Best JA, Chen Y, Nagamoto-Combs K, Osterhout CA, and Tank AW. 2001. The cAMP responsive element and CREB partially mediate the response of the tyrosine hydroxylase gene to phorbol ester. J Neurochem. Mar;76(5):1376-1385.

Sterling CR and Tank AW. 2001. Adrenal tyrosine hydroxylase activity and gene expression are increased by intraventricular administration of nicotine. J Pharmacol Exp Ther. Jan;296(1):15-21.