We have demonstrated that the activation of beta-adrenergic receptors (BAR) by the lipophilic BAR agonist clenbuterol increases NGF biosynthesis in rat cerebral cortex and in C6-2B glioma cells (glial phenotype). The increase in NGF mRNA is due to increased gene expression. I will extend these studies by using various BAR agonists and antagonists (acute or protracted treatments) in adult and 2 year old rats. Neuroanatomical correlates will be used to establish whether NGF, induced pharmacologically, exerts physiological effects. C6-2B rat glioma cells will be used to characterize signal transduction mechanisms (activation of protein kinases A and C) and steroid receptors operative in the regulation of NGF biosynthesis in glial cells. These studies will be complemented by experiments aimed to test whether transcriptional factors which contribute to the tissue specific regulation of NGF expression, are induced or activated (following the proposed pharmacological manipulations) in glial and/or neuronal cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Modified Research Career Development Award (K04)
Project #
5K04NS001675-03
Application #
2259729
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1993-08-01
Project End
1998-07-31
Budget Start
1995-08-01
Budget End
1996-07-31
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Georgetown University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
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