Nerve growth factor (NGF) is present in the central nervous system and has specific, neurotrophic effects on cholinergic neurons of the basal forebrain which are known to degenerate during Alzheimer's disease. To understand the regulation of NGF expression in the brain, we are interested in detaining whether glial cells or neurons that communicate with cholinergic neurons, or both, produce NGF. The proposed work is based on the finding that a number of cell types and tissues that produce NGF in vivo produce greatly elevated levels of NGF in vitro. This allowed the detection of NGF produced by the iris, heart and sciatic nerve before techniques were developed that were sensitive enough to detect NGF produced by these sources in vivo. Glial cells have recently been shown to produce elevated levels of NGF in culture compared to the levels of NGF normally found in the brain. The proposed study will characterize the expression of NGF in glial and neuronal cells cultured from the brain to develop their relationship to normal NGF expression in the brain. This will lead to a better understanding of which cell types produce NGF and how the regulation of NGF expression by these cells will be modulated, ultimately for therapeutic purposes.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Unknown (R35)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Irvine
United States
Zip Code
Cribbs, D H; Pike, C J; Weinstein, S L et al. (1997) All-D-enantiomers of beta-amyloid exhibit similar biological properties to all-L-beta-amyloids. J Biol Chem 272:7431-6
Gomez-Pinilla, F; Miller, S; Choi, J et al. (1997) Heparan sulfate potentiates the autocrine action of basic fibroblast growth factor in astrocytes: an in vivo and in vitro study. Neuroscience 76:137-45
Ulas, J; Cotman, C W (1997) Decreased expression of N-methyl-D-aspartate receptor 1 messenger RNA in select regions of Alzheimer brain. Neuroscience 79:973-82
Su, J H; Cummings, B J; Cotman, C W (1996) Plaque biogenesis in brain aging and Alzheimer's disease. I. Progressive changes in phosphorylation states of paired helical filaments and neurofilaments. Brain Res 739:79-87
Ulas, J; Cotman, C W (1996) Dopaminergic denervation of striatum results in elevated expression of NR2A subunit. Neuroreport 7:1789-93
Cribbs, D H; Kreng, V M; Anderson, A J et al. (1996) Cross-linking of concanavalin A receptors on cortical neurons induces programmed cell death. Neuroscience 75:173-85
Anderson, A J; Su, J H; Cotman, C W (1996) DNA damage and apoptosis in Alzheimer's disease: colocalization with c-Jun immunoreactivity, relationship to brain area, and effect of postmortem delay. J Neurosci 16:1710-9
Cummings, B J; Head, E; Afagh, A J et al. (1996) Beta-amyloid accumulation correlates with cognitive dysfunction in the aged canine. Neurobiol Learn Mem 66:11-23
Kesslak, J P; Yuan, D; Neeper, S et al. (1995) Vulnerability of the hippocampus to kainate excitotoxicity in the aged, mature and young adult rat. Neurosci Lett 188:117-20
Araujo, D M; Cotman, C W (1995) Differential effects of interleukin-1 beta and interleukin-2 on glia and hippocampal neurons in culture. Int J Dev Neurosci 13:201-12

Showing the most recent 10 out of 59 publications