Journal of Neural Transmission

, Volume 113, Issue 7, pp 813–820

Chronic alcohol intoxication in rats leads to a strong but transient increase in NGF levels in distinct brain regions

  • C. A. Gericke
  • O. Schulte-Herbrüggen
  • T. Arendt
  • R. Hellweg


Nerve growth factor (NGF), a member of the neurotrophin family, is an essential mediator of neuronal activity and synaptic plasticity of basal forebrain cholinergic neurons. In this study NGF-protein levels were determined in areas of the basal forebrain cholinergic system, its projection areas as well as the striatum and the cerebellum after long-term exposure (6 and 9 months) to ethanol and a phase of withdrawal in male Sprague-Dawley rats. 6-month alcohol treatment led to an increase of NGF to 650–850% of controls in the basal forebrain and the septum and to a 210–485% increase in the cholinergic projection areas (anterior cortex, hippocampus and olfactory bulb). After 9 months exposure to ethanol, a decrease of NGF by 16% in the frontal cortex was observed compared to controls. In the other brain regions no differences in NGF expression were detectable at this time-point. These results support the idea of an endogenous neuroprotective mechanism acting through a transient NGF induction followed by a decrease in NGF-levels during the course of further neuronal degeneration.

Keywords: NGF, basal forebrain, cholinergic degeneration, ethanol. 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aloe, L, Tirassa, P 1992The effect of long-term alcohol intake on brain NGF-target cells of aged ratsAlcohol9299304PubMedCrossRefGoogle Scholar
  2. Altar, CA 1991Nerve growth factor and the neostriatumProg Neuropsychopharmacol Biol Psychiatry15157169PubMedCrossRefGoogle Scholar
  3. Arendt, T, Bigl, V, Arendt, A, Tennstedt, A 1983Loss of neurons in the nucleus basalis of Meynert in Alzheimers-disease, Paralysis agitans and Korsakoffs diseaseActa Neuropathol61101108PubMedCrossRefGoogle Scholar
  4. Arendt, T, Allen, Y, Sinden, J, Schugens, MM, Marchbanks, RM, Lantos, PL, Gray, JA 1988Cholinergic-rich brain transplants reverse alcohol-induced memory deficitsNature332448450PubMedCrossRefGoogle Scholar
  5. Arendt, T, Allen, Y, Marchbanks, RM, Schugens, MM, Sinden, J, Lantos, PL, Gray, JA 1989Cholinergic system and memory in the rat – effects of chronic ethanol, embryonic basal forebrain brain transplants and excitotoxic lesions of cholinergic basal forebrain projection systemNeuroscience33435462PubMedCrossRefGoogle Scholar
  6. Arendt, T, Brückner, MK, Pagliusi, S, Krell, T 1995aDegeneration of rat cholinergic basal forebrain neurons and reactive changes in nerve growth factor expression after chronic neurotoxic injury. I. Degeneration and plastic response of basal forebrain neuronsNeuroscience65633645CrossRefGoogle Scholar
  7. Arendt, T, Brückner, MK, Krell, T, Pagliusi, S, Kruska, L, Heumann, R 1995bDegeneration of rat cholinergic basal forebrain neurons and reactive changes in nerve growth factor expression after chronic neurotoxic injury. II. Reactive expression of the nerve growth factor gene in astrocytesNeuroscience65647659CrossRefGoogle Scholar
  8. Arendt, T, Marcova, L, Bigl, V, Brückner, MK 1995cDendritic reorganization in the basal forebrain under degenerative conditions and its defects in Alzheimers-disease. 1. Dendritic organization of the normal human basal forebrainJ Comp Neurol351169188CrossRefGoogle Scholar
  9. Beracochea, D, Lescaudron, L, Verna, A, Jaffard, R 1987Neuroanatomical effects of chronic ethanol consumption on dorsomedial and anterior thalamic nuclei and on substantia innominata in miceNeurosci Lett738184PubMedCrossRefGoogle Scholar
  10. Cadete-Leite, A, Pereira, PA, Madeira, MD, Paula-Barbosa, MM 2003Nerve growth factor prevents cell death and induces hypertrophy of basal forebrain cholinergic neurons in rats withdrawn from prolonged ethanol intakeNeuroscience11910551069PubMedCrossRefGoogle Scholar
  11. Cooper, JD, Lindholm, D, Sofroniew, MV 1994Reduced transport of [125I] nerve growth factor by cholinergic neurons and down-regulated TrkA expression in the medial septum of aged ratsNeuroscience62625629PubMedCrossRefGoogle Scholar
  12. Counts, SE, Nadeem, M, Wuu, J, Ginsberg, SD, Saragovi, HU, Mufson, EJ 2004Reduction of cortical TrkA but not p75 (NTR) protein in early-stage Alzheimer’s diseaseAnn Neurol56520531PubMedCrossRefGoogle Scholar
  13. Crutcher, KA, Scott, SA, Liang, S, Everson, WV, Weingartner, J 1993Detection of NGF-like activity in human brain tissue: increased levels in Alzheimer’s diseaseJ Neurosci1325402550PubMedGoogle Scholar
  14. De Lacalle, S, Cooper, JD, Svendsen, CN, Dunnett, SB, Sofroniew, MV 1996Reduced retrograde labelling with fluorescent tracer accompanies neuronal atrophy of basal forebrain cholinergic neurons in aged ratsNeuroscience751927PubMedCrossRefGoogle Scholar
  15. De Simone, R, Aloe, L 1993Influence of ethanol consumption on brain nerve growth factor and its target cells in developing and adult rodentsAnn Ist Super Sanità29179183PubMedGoogle Scholar
  16. Durkin, T 1989Central cholinergic pathways and learning and memory processes: presynaptic aspectsComp Biochem Physiol A93273280PubMedCrossRefGoogle Scholar
  17. Fahnestock, M, Scott, SA, Jette, N, Weingartner, JA, Crutcher, KA 1996Nerve growth factor mRNA and protein levels measured in the same tissue from normal and Alzheimer’s disease parietal cortexMol Brain Res42175178PubMedCrossRefGoogle Scholar
  18. Hellweg, R, Hock, C, Hartung, HD 1989An improved rapid and highly sensitive enzyme immunoassay for nerve growth factor. TechniqueJ Methods Cell Mol Biol14349Google Scholar
  19. Hellweg, R, Nitsch, R, Hock, C, Jaksch, M, Hoyer, S 1992Nerve growth-factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy-metabolismJ Neurosci Res31479486PubMedCrossRefGoogle Scholar
  20. Hellweg, R, Baethge, C, Hartung, HD, Brückner, MK, Arendt, T 1996NGF level in the rat sciatic nerve is decreased after long-term consumption of ethanolNeuroreport7777780PubMedGoogle Scholar
  21. Hellweg, R, Gericke, CA, Jendroska, K, Hartung, HD, Cervos-Navarro, J 1998NGF content in the cerebral cortex of non-demented patients with amyloid-plaques and in symptomatic Alzheimer’s diseaseInt J Dev Neurosci16787794PubMedCrossRefGoogle Scholar
  22. Hörtnagl, H, Hanin, I 1992

    Toxins affecting the cholinergic system

    Herken, HHucho, F eds. Selective neurotoxicitySpringerBerlin Heidelberg New York293332
    Google Scholar
  23. Hörtnagl, H, Hellweg, R 1997Insights into the role of the cholinergic component of the septohippocampal pathway: what have we learned from experimental lesion studies?Brain Res Bull43245255PubMedCrossRefGoogle Scholar
  24. Korsching, S, Thoenen, H 1987Two-site enzyme immunoassay for nerve growth factorMeth Enzymol147167185PubMedGoogle Scholar
  25. Lindvall, O, Kokaia, Z, Bengzon, J, Elmer, E, Kokaia, M 1994Neurotrophins and brain insultsTrends Neurosci17490496PubMedCrossRefGoogle Scholar
  26. Lukoyanov, NV, Sa, MJ, Madeira, MD, Paula-Barbosa, MM 2004Selective loss of hilar neurons and impairment of initial learning in rats after repeated administration of electroconvulsive shock seizuresExp Brain Res154192200PubMedCrossRefGoogle Scholar
  27. Mattson, MP, Scheff, SW 1994Endogenous neuroprotection factors and traumatic brain injury: mechanisms of action and implications for therapyJ Neurotrauma11333PubMedCrossRefGoogle Scholar
  28. Miller, MW, Mooney, MS 2004aChronic exposure to ethanol alters neurotrophin content in the basal forebrain-cortex system in the mature rat: effects on aoto-paracrine mechanismsJ Neurobiol60490498CrossRefGoogle Scholar
  29. Miller, MW 2004bRepeated episodic exposure to ethanol affects neurotrophin content in the forebrain of the mature ratExp Neurol189173181CrossRefGoogle Scholar
  30. Paula-Barbosa, MM, Pereira, PA, Cardoso, A, Madeira, MD, Cadete-Leite, A 2004The effects of nerve growth factor upon the neuropeptide content of the suprachiasmatic nucleus of rats withdrawn from ethanol are mediated by the nucleus basalis magnocellularisJ Neurocytol33453463PubMedGoogle Scholar
  31. Sarter, MF, Bruno, JP 1994Cognitive functions of cortical ACh: lessons from studies on trans-synaptic modulation of activated effluxTrends Neurosci17217221PubMedCrossRefGoogle Scholar
  32. Scott, SA, Mufson, EJ, Weingartner, JA, Skau, KA, Crutcher, KA 1995Nerve growth factor in Alzheimer’s disease: increased levels throughout the brain coupled with declines in nucleus basalisJ Neurosci1562136221PubMedGoogle Scholar
  33. Thoenen, H, Bandtlow, C, Heumann, R 1987The physiological function of nerve growth factor in the central nervous system: comparison with the peripheryRev Physiol Biochem Pharmacol109145178PubMedCrossRefGoogle Scholar
  34. Wenk, GL, Willard, LB 1998The neural mechanisms underlying cholinergic cell death within the basal forebrainInt J Dev Neurosci16729735PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • C. A. Gericke
    • 1
  • O. Schulte-Herbrüggen
    • 2
  • T. Arendt
    • 4
  • R. Hellweg
    • 3
  1. 1.Institute of Health SciencesBerlin University of TechnologyBerlinGermany
  2. 2.Department of NeurologyCharité-University Medicine Berlin, Campus Benjamin Franklin, Humboldt-University and Free University of BerlinGermany
  3. 3.Department of Psychiatry and PsychotherapyCharité-University Medicine Berlin, Campus Benjamin Franklin, Humboldt-University and Free University of BerlinGermany
  4. 4.Paul Flechsig Institute of Brain Research, Department of NeuroanatomyUniversity of LeipzigGermany

Personalised recommendations