Abstract

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.

  Funding Agency

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

  Institution

Name
Georgetown University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057

  Publications

Leritz, Elizabeth; Brandt, Jason; Minor, Melissa et al. (2002) Neuropsychological functioning and its relationship to antiphospholipid antibodies in patients with systemic lupus erythematosus. J Clin Exp Neuropsychol 24:527-33
Leritz, E; Brandt, J; Minor, M et al. (2000) ""Subcortical"" cognitive impairment in patients with systemic lupus erythematosus. J Int Neuropsychol Soc 6:821-5
Colangelo, A M; Follesa, P; Mocchetti, I (1998) Differential induction of nerve growth factor and basic fibroblast growth factor mRNA in neonatal and aged rat brain. Brain Res Mol Brain Res 53:218-25
Teng, Y D; Mocchetti, I; Wrathall, J R (1998) Basic and acidic fibroblast growth factors protect spinal motor neurones in vivo after experimental spinal cord injury. Eur J Neurosci 10:798-802
Shi, B; Rabin, S J; Brandoli, C et al. (1998) Dexamethasone induces hypertrophy of developing medial septum cholinergic neurons: potential role of nerve growth factor. J Neurosci 18:9326-34
Brandoli, C; Sanna, A; De Bernardi, M A et al. (1998) Brain-derived neurotrophic factor and basic fibroblast growth factor downregulate NMDA receptor function in cerebellar granule cells. J Neurosci 18:7953-61
Marini, A M; Rabin, S J; Lipsky, R H et al. (1998) Activity-dependent release of brain-derived neurotrophic factor underlies the neuroprotective effect of N-methyl-D-aspartate. J Biol Chem 273:29394-9
Colangelo, A M; Johnson, P F; Mocchetti, I (1998) beta-adrenergic receptor-induced activation of nerve growth factor gene transcription in rat cerebral cortex involves CCAAT/enhancer-binding protein delta. Proc Natl Acad Sci U S A 95:10920-5
Rabin, S J; Tornatore, C; Baker-Cairns, B et al. (1998) TrkA receptors delay C6-2B glioma cell growth in rat striatum. Brain Res Mol Brain Res 56:273-6
Follesa, P; Wrathall, J R; Mocchetti, I (1998) 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline (NBQX) increases fibroblast growth factor mRNA levels after contusive spinal cord injury. Brain Res 782:306-9

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