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Volume 16, Number 21, Issue of November 1, 1996 pp. 6665-6675
Copyright ©1996 Society for Neuroscience

Neurotrophin Effects on Survival and Expression of Cholinergic Properties in Cultured Rat Septal Neurons under Normal and Stress Conditions

Received Jan. 22, 1996; revised Aug. 5, 1996; accepted Aug. 9, 1996.

Doris Nonner, Ellen F. Barrett, and John N. Barrett

Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33101

These studies tested the hypothesis that survival-promoting effects of neurotrophins on basal forebrain cholinergic neurons are enhanced under stress. Septal neurons from embryonic day 14-15 rats exposed for 10-14 d to neurotrophin [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4 (NT-4), each at 100 ng/ml] showed a two- to threefold increase in choline acetyltransferase (ChAT) activity, with little evidence of synergistic interactions. Neurotrophins produced no significant increase in the survival of total or acetylcholinesterase (AChE)-positive neurons at moderate plating density (1200-1600 cells/mm²). However, with very low plating densities (2-28 cells/mm²) BDNF, NT-3, and NT-4 (but not NGF) increased total neuronal survival, and BDNF increased survival of AChE-positive neurons.

NGF and BDNF enhanced ChAT activity and survival of cholinergic neurons after a 24 hr hypoglycemic stress, even when added 1 hr after stress onset. All four tested neurotrophins increased total neuronal survival after hypoglycemic stress. These results suggest that neurotrophins are important for preservation of central cholinergic function under stress conditions, with different neurotrophins protecting against different stresses. The stress-associated survival-promoting effects of neurotrophins were not limited to the cholinergic subpopulation.

Key words: basal forebrain; septum; central cholinergic neurons; neurotrophins; hypoglycemia; stress protection; nerve growth factor; brain-derived neurotrophic factor; neurotrophin-3; neurotrophin-4; choline acetyltransferase; neuronal survival

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