Effects of Nerve Growth Factor on Cholinergic Neurons of the Rat Forebrain

  • F. Hefti
  • J. Hartikka
  • B. Will
Part of the Advances in Behavioral Biology book series (ABBI, volume 28)


Nerve growth factor (NGF) is essential for development and function of peripheral sympathetic and sensory neurons (Thoenen and Barde, 1980). Administration of NGF to rodents produces hypertrophy of sympathetic neurons, whereas treatment with antibodies to NGF results in atrophy. Furthermore, NGF selectively stimulates the production of enzymes specific for the synthesis of catecholamine transmitters in sympathetic neurons. In contrast to these pronounced effects on peripheral sympathetic neurons, central catecholaminergic neurons are not affected by NGF or antibodies to NGF (Dreyfus et al., 1980; Konkol et al., 1978; Schwab et al., 1979). However, the following observations have suggested that NGF may play a role in the function of central cholinergic neurons located in septum and nucleus basalis and projecting to hippocampus and cortex. First, NGF injected into these cholinergic target areas is specifically taken up by cholinergic nerve terminals and is transported retrogradly to their cell bodies in septum and nucleus basalis (Schwab et al., 1979; Seiler and Schwab, 1984).


Nerve Growth Factor Cholinergic Neuron Nucleus Basalis Lesion Side ChAT Activity 
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  1. Appel, S.H., 1981, A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer’s disease, Ann. Neurol. 10:499.CrossRefGoogle Scholar
  2. Björklund, A. and Stenevi, U., 1977, Reformation of the severed septo-hippocampal cholinergic pathway in the adult rat by transplanted septal neurons, Cell. Tiss. Res., 185:289.CrossRefGoogle Scholar
  3. Crutcher, K.A., Brothers, L. and Davis, J.N., 1979, Sprouting of sympathetic nerves in the absence of afferent input, Exp. Neurol. 66:778.CrossRefGoogle Scholar
  4. Crutcher, K.A. and Collins, F. 1982, In vitro evidence for two distinct hippocampal growth factors: basis of neuronal plasticity? Science 217:67.CrossRefGoogle Scholar
  5. Crutcher, K.A. and Davis, J.N., 1981, Sympathetic noradrenergic sprouting in response to central cholinergic denervation, Trends Neurosci., 4:70.CrossRefGoogle Scholar
  6. Dreyfus, C.F., Peterson, E.R. and Crain, S.M., 1980, Failure of nerve growth factor to affect fetal mouse brain stem catecholaminergic neurons in culture, Brain Res., 194:540.CrossRefGoogle Scholar
  7. Gnahn, H., Hefti, F., Heumann, R., Schwab, M.E. and Thoenen, H., 1983, NGF-mediated increase of choline acetyltransferase (ChAT) in the neonatal rat forebrain; evidence for a physiological role of NGF in the brain? Develop. Brain Res., 9:45.CrossRefGoogle Scholar
  8. Hart, T., Chaimas, N., Moore, R.Y. and Stein, D., 1978, Effects of nerve growth factor on behavioral recovery following caudate nucleus lesions in rats, Brain Res. Bull., 3:245.CrossRefGoogle Scholar
  9. Hefti, F., 1983, Alzheimer’s disease caused by a lack of nerve growth factor?, Ann. Neurol., 13:109.CrossRefGoogle Scholar
  10. Hefti, F., Dravid, A. and Hartikka J., 1984a, Chronic intraventricular injections of nerve growth factor elevate hippocampal choline acetyltransferase activity in adult rats with partial septo-hippocampal lesions, Brain Res., 293:305.CrossRefGoogle Scholar
  11. Hefti, F., Hartikka, J., Eckenstein, F., Gnahn, H., Heumann, R. and Schwab, M. 1984b, Nerve growth factor (NGF) increases choline acetyltransferase but not survival or fiber outgrowth of cultured septal cholinergic neurons, Neurosci., in press.Google Scholar
  12. Honegger, P. and Lenoir, D., 1982, Nerve growth factor (NGF) stimulation of cholinergic telencephalic neurons in aggregating cell cultures, Develop. Brain Res., 3:229.CrossRefGoogle Scholar
  13. König, J.F.R. and Klippel, R.A., 1963, “The Rat Brain. A Stereotaxic Atlas of the Forebrain and Lower Parts of the Brain Stem”, Williams and Wilkins, Baltimore, MD.Google Scholar
  14. Konkol, R.J., Mailman, R.B., Bebdeich, E.G., Garrison, A.M., Müller, R.A. and Breese, G.R., 1978, Evaluation of the effects of nerve growth factor and anti-nerve growth factor on the development of central cate-cholamine-containing neurons, Brain Res., 144:277.CrossRefGoogle Scholar
  15. Leis, T., Pallage, V., Toniolo, G. and Will, B., 1984, Working memory theory of hippocampal function needs qualification, Behav. Neural. Biol., 42:140.CrossRefGoogle Scholar
  16. Loy, R. and Moore, R.Y., 1977, Anomalous innervation of the hippocampal formation by peripheral sympathetic axons following mechanical injury, Exp. Neurol., 57:645.CrossRefGoogle Scholar
  17. Meibach, R.C. and Siegel, A., 1977, Efferent connections of the septal area in the rat: an analysis utilizing retrograde and anterograde transport methods, Brain Res., 119:1.CrossRefGoogle Scholar
  18. Nadler, J.V., Mattews, D.A., Cotman, C.W. and Lynch, G.S., 1974, Development of cholinergic innervation in the hippocampal formation of the rat, Develop. Biol., 36: 142.CrossRefGoogle Scholar
  19. Rossor, M.N., Svendsen, C., Hunt, S.P., Mountjoy, C.Q., Roth, M. and Iversen, L.L., 1982, The substantia innominata in Alzheimer’s disease: an histochemical and biochemical study of cholinergic marker enzymes, Neurosci. Lett., 28:217.CrossRefGoogle Scholar
  20. Ruegg, U.T. and Hefti, F., 1984, Growth of dissociated neurons in culture dishes coated with synthetic polymeric amines, Neurosci. Lett., 49:319.CrossRefGoogle Scholar
  21. Schwab, M.E., Otten, U., Agid, Y. and Thoenen, H., 1979, Nerve growth factor (NGF) in the rat CNS: absence of specific retrograde axonal transport on tyrosine hydroxylase induction in locus coeruleus and substantia nigra, Brain Res., 168:473.CrossRefGoogle Scholar
  22. Seiler, M. and Schwab, M.E., 1984, Specific retrograde transport of nerve growth factor (NGF) from neocortex to nucleus basalis in the rat. Brain Res., 300:33.CrossRefGoogle Scholar
  23. Segal, M. and Landis, S., 1979, Afferents of the hippocampus of the rat studied with the method of retrograde transport of horseradish peroxidase, Brain Res., 78:1.CrossRefGoogle Scholar
  24. Stein, D.G., Deluzarche, F.M. and Will, B., 1984, Nerve growth factor improves radial maze performance in adult rats with hippocampal lesions, in preparation.Google Scholar
  25. Stenevi, U. and Björklund, A., 1978, Growth of vascular sympathetic axons into the hippocampus after lesions of the septo-hippocampal pathway: a pitfall in brain lesion studies, Neurosci. Lett., 7:219.CrossRefGoogle Scholar
  26. Terry, R.D. and Davies, P., 1980, Dementia of the Alzheimer type, Ann. Rev. Neurosci., 3:77.CrossRefGoogle Scholar
  27. Thoenen, H. and Barde, Y.A., 1980, Physiology of nerve growth factor, Physiol. Rev., 60:1284.Google Scholar
  28. Whitehouse, P.J., Price, D.L., Stroble, R.G., Clark, A.W., Coyle, J.T. and DeLong, M.R., 1982, Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain, Science, 215:1237.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • F. Hefti
    • 1
  • J. Hartikka
    • 1
  • B. Will
    • 2
  1. 1.Preclinical ResearchSandoz Ltd.BasleSwitzerland
  2. 2.Laboratoire de Neurobiologie des ComportementsUniversité Louis PasteurStrasbourgFrance

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