Abstract

The neurotransmitter substance P (SP) is implicated in a number of neurological disorders, yet the regulation of the SP-encoding preprotachykinin (PPT) gene is poorly understood. Using organotypic brain slice cultures, particle-mediated gene transfection, quantitative confocal microscopic analysis and site specific mutagenesis, we will identify the gene regulatory elements mediating neuron-specific expression and the response to dopamine and other stimuli. For the first time, PPT promoter activity will be quantified within single, living PPT-expressing neurons. Ultimately, the ability to modify substance P neurotransmission at the transcriptional level may constitute a novel therapeutic target for the treatment of Parkinson's disease and other movement disorders, chronic pain, anxiety and depression, addiction and other neuropsychiatric disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034935-12
Application #
6393773
Study Section
Special Emphasis Panel (ZRG1-MDCN-5 (01))
Program Officer
Oliver, Eugene J
Project Start
1995-06-01
Project End
2004-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
12
Fiscal Year
2001
Total Cost
$260,750
Indirect Cost

  Institution

Name
Wayne State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202

  Publications

Sin, Mihaela; Michelhaugh, Sharon K; Bannon, Michael J (2008) D1 receptor regulation of preprotachykinin-A gene by extracellular signal-regulated kinase pathway in striatal cultures. Neuroreport 19:187-91
Calin-Jageman, Irina E; Wang, Jun; Bannon, Michael J (2006) Regulation of the preprotachykinin-I gene promoter through a protein kinase A-dependent, cyclic AMP response element-binding protein-independent mechanism. J Neurochem 97:255-64
Sin, Mihaela; Walker, Paul D; Bouhamdan, Mohamad et al. (2005) Preferential expression of an AAV-2 construct in NOS-positive interneurons following intrastriatal injection. Brain Res Mol Brain Res 141:74-82
Bannon, M J; Michelhaugh, S K; Wang, J et al. (2001) The human dopamine transporter gene: gene organization, transcriptional regulation, and potential involvement in neuropsychiatric disorders. Eur Neuropsychopharmacol 11:449-55
Walker, P D; Andrade, R; Quinn, J P et al. (2000) Real-time analysis of preprotachykinin promoter activity in single cortical neurons. J Neurochem 75:882-5
Hahn, M K; Bannon, M J (1999) Stress-induced C-fos expression in the rat locus coeruleus is dependent on neurokinin 1 receptor activation. Neuroscience 94:1183-8
Sacchetti, P; Brownschidle, L A; Granneman, J G et al. (1999) Characterization of the 5'-flanking region of the human dopamine transporter gene. Brain Res Mol Brain Res 74:167-74
Burchett, S A; Bannon, M J; Granneman, J G (1999) RGS mRNA expression in rat striatum: modulation by dopamine receptors and effects of repeated amphetamine administration. J Neurochem 72:1529-33
Hahn, M K; Bannon, M J (1998) Tachykinin NK1 receptor antagonists enhance stress-induced c-fos in rat locus coeruleus. Eur J Pharmacol 348:155-60
Bannon, M J; Whitty, C J (1997) Age-related and regional differences in dopamine transporter mRNA expression in human midbrain. Neurology 48:969-77

Showing the most recent 10 out of 12 publications