Abstract
In aged rodents, impairments in learning and memory have been associated with an age-dependent decline in forebrain of cholinergic function1, and recent evidence indicates that the cholinergic neurons in the nucleus basalis magnocellularis, the septal-diagonal band area and the striatum undergo age-dependent atrophy2–5. Thus, as in Alzheimer-type dementia in man, degenerative changes in the forebrain cholinergic system may contribute to age-related cognitive impairments in rodents. The cause of these degenerative changes is not known. Recent studies have shown that the central cholinergic neurons in the septal–diagonal band area, nucleus basalis and striatum are sensitive to the neurotrophic protein nerve growth factor (NGF)6–10. In particular, intraventricular injections or infusions of NGF in young adult rats have been shown to prevent retrograde neuronal cell death11–13 and promote behavioural recovery after damage to the septo–hippocampal connections14. It is so far not known, however, whether the atrophic cholinergic neurons in aged animals are responsive to NGF treatment. We report here that continuous intracerebral infusion of NGF over a period of four weeks can partly reverse the cholinergic cell body atrophy and improve retention of a spatial memory task in behaviourally impaired aged rats.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bartus, R. T., Dean, R. L., Beer, B. & Lippa, A. S. Science 217, 408–416 (1982).
Hornberger, J. C., Buell, S. J., Flood, D. G., McNeill, T. H. & Coleman, P. D. Neurobiol. Aging 6, 269–275 (1985).
Biegon, A., Greenberger, V. & Segal, M. Neurobiol. Aging 7, 215–217 (1986).
Luine, V. N., Renner, K. J., Heady, S. & Jones, K. J. Neurobiol. Aging 7, 193–198 (1986).
Albanese, A., AltaVista, M. C., Rossi, P., Iacopino, C. & Gozzo, S. Neurosci. Lett. 26, S88 (1986).
Schwab, M. E., Otten, U., Agid, Y. & Thoenen, H. Brain Res. 168, 473–483 (1979).
Gnahn, H., Hefti, F., Heumann, R., Schwab, M. E. & Thoenen, H. Devl Brain Res. 9, 45–52 (1983).
Hefti, F., Hartikka, F., Eckenstein, H., Gnahn, R., Heumann, R. & Schwab, M. Neuroscience 14, 55–68 (1985).
Mobley, W. C., Rutkowski, J. L., Tennekoon, G. I., Buchana, K. & Johnston, M. V. Science 229, 284–286 (1985).
Richardson, P. M., Verge Issa, V. M. K. & Riopelle, R. J. J. Neurosci. 6, 2312–2321 (1986).
Hefti, F. J. Neurosci. 6, 2155–2162 (1986).
Williams, L. R. et al. Proc. natn. Acad. Sci. U.S.A. 89, 9231–9235 (1987).
Kromer, L. F. Science 235, 214–216 (1987).
Will, B. & Hefti, F. Behav. Brain Res. 17, 17–24 (1985).
Gage, F. H., Björklund, A., Stenevi, U., Dunnett, S. B. & Kelly, P. A. T. Science 225, 533–536 (1984).
Gage, F. H., Kelly, P. A. T. & Björklund, A. J. Neurosci. 4, 2856–2866 (1984).
Morris, R. G. M. J. Neurosci. Meth. 11, 47–60 (1984).
Williams, L. R. et al. Expl Neurol. 95, 743–754 (1987).
Butcher, L. L. in Handbook of Chemical Neuroanatomy Vol. 1 (eds Björklund, A. & Hökfelt, T.) 1–49 (Elsevier, Amsterdam, 1983).
Woolf, N. J., Hernit, M. C. & Butcher, L. L. Neurosci. Lett. 66, 281–286 (1986).
Sutherland, R. J., Whishaw, I. Q. & Regehr, J. C. J. Comp. physiol. Psychol. 96, 563–573 (1982).
Wishaw, I. Q., O'Connor, W. T. & Dunnett, S. B. Behav. Brain Res. 17, 103–115 (1985).
Gage, F. H. & Björklund, A. A. Rev. Physiol. 48, 447–459 (1986).
Appel, S. H. Ann. Neurol. 10, 499–505 (1981).
Hefti, F. & Weiner, W. J. Ann. Neurol. 20, 275–281 (1986).
Sofroniew, M. V., Pearson, R. C. A., Eckenstein, F., Cuello, A. C. & Powell, T. P. S. Brain Res. 289, 370–374 (1983).
Sofroniew, M. V., Isacson, O. & Björklund, A. Brain Res. 378, 409–415 (1986).
Geneser-Jensen, F. A. & Blackstad, T. W. Z. Zellforsch. mikrosk. Anat. 144, 693–720 (1971).
Gage, F. H., Wictorin, K., Fischer, W., Williams, L. R., Varon, S. & Björklund, A. Neuroscience 19, 241–256 (1986).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fischer, W., Wictorin, K., Björklund, A. et al. Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor. Nature 329, 65–68 (1987). https://doi.org/10.1038/329065a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/329065a0
This article is cited by
-
Genetic Phenotypes of Alzheimer’s Disease: Mechanisms and Potential Therapy
Phenomics (2023)
-
The effect of nerve growth factor on supporting spatial memory depends upon hippocampal cholinergic innervation
Translational Psychiatry (2021)
-
Modulation of the p75 neurotrophin receptor suppresses age-related basal forebrain cholinergic neuron degeneration
Scientific Reports (2019)
-
The Role of Estrogen in Brain and Cognitive Aging
Neurotherapeutics (2019)
-
A bi-objective study of the minimum latency problem
Journal of Heuristics (2019)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.