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NGF is a neurotrophic factor for basal forebrain cholinergic neurons and may serve to counteract the cholinergic deficits that are observed in Alzheimer's disease. Prior to the introduction of clinical trials, it is essential that recombinant human NGF (rhNGF) be produced and that its actions on target cells in the CNS be demonstrated. We prepared rhNGF and examined its actions on fetal rat brain neurons in culture including, in particular, the cholinergic neurons of the basal forebrain. rhNGF was more potent in increasing choline acetyltransferase (ChAT) activity in septal cultures than NGF purified from mouse salivary glands (mNGF). ED50s of the beta-NGF dimers were 4.9 pM for rhNGF and 12.4 pM for mNGF. The maximal ChAT activity response was achieved at approximately 35 pM with both NGFs and their efficacies were not significantly different. The two NGFs were not additive in effect. Identical to the results with mNGF, rhNGF strongly enhanced the intensity of ChAT immunostaining in septal cultures. Neither rhNGF nor mNGF affected the appearance of the cultures under phase-contrast illumination. Survival of cells at very low plating density on polyornithine/laminin-coated culture dishes was not affected by rhNGF or mNGF. Protein content and the uptake of GABA were also unaffected. At concentrations of up to 10 micrograms/ml, rhNGF did not significantly increase uptake of dopamine into cultures of ventral mesencephalon. We conclude that rhNGF produces potent and selective actions on cholinergic neurons of the basal forebrain as previously shown for mNGF.
B Knüsel, and
L E Burton, and
F M Longo, and
W C Mobley, and
V E Koliatsos, and
D L Price, and
F Hefti
January 1991,
Neuroscience letters,
B Knüsel, and
L E Burton, and
F M Longo, and
W C Mobley, and
V E Koliatsos, and
D L Price, and
F Hefti
August 1993,
The European journal of neuroscience,
B Knüsel, and
L E Burton, and
F M Longo, and
W C Mobley, and
V E Koliatsos, and
D L Price, and
F Hefti
January 1988,
The Journal of neuroscience : the official journal of the Society for Neuroscience,
B Knüsel, and
L E Burton, and
F M Longo, and
W C Mobley, and
V E Koliatsos, and
D L Price, and
F Hefti
January 2016,
Journal of biological regulators and homeostatic agents,
B Knüsel, and
L E Burton, and
F M Longo, and
W C Mobley, and
V E Koliatsos, and
D L Price, and
F Hefti
November 1975,
Nature,
B Knüsel, and
L E Burton, and
F M Longo, and
W C Mobley, and
V E Koliatsos, and
D L Price, and
F Hefti
December 1994,
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B Knüsel, and
L E Burton, and
F M Longo, and
W C Mobley, and
V E Koliatsos, and
D L Price, and
F Hefti
September 1991,
Gut,
B Knüsel, and
L E Burton, and
F M Longo, and
W C Mobley, and
V E Koliatsos, and
D L Price, and
F Hefti
May 1994,
Biological & pharmaceutical bulletin,
B Knüsel, and
L E Burton, and
F M Longo, and
W C Mobley, and
V E Koliatsos, and
D L Price, and
F Hefti
January 1990,
Biochemistry international,
B Knüsel, and
L E Burton, and
F M Longo, and
W C Mobley, and
V E Koliatsos, and
D L Price, and
F Hefti
July 1988,
Proceedings of the National Academy of Sciences of the United States of America,
