Neurochemical Research

, Volume 30, Issue 2, pp 185–190 | Cite as

Short- and Long-term Memory are Differentialy Modulated by Hippocampal Nerve Growth Factor and Fibroblast Growth Factor

  • Roger Walz
  • Rafael Roesler
  • Adalisa Reinke
  • Márcio Rodrigo Martins
  • João QuevedoEmail author
  • Ivan Izquierdo

Rats were implanted with cannulae in the CA1 area of the dorsal hippocampus and trained in one-trial step-down inhibitory avoidance. Two retention tests were carried out in each animal, one at 1.5 h to measure short-term memory (STM) and another at 24 h to measure long-term memory (LTM). The purpose of the present study was to evaluate the modulation on hippocampal nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) on short- and long-term memory. Immediately after training, animals received 5 μl of NGF (0.05, 0.5 or 5.0 ng), bFGF (1.25, 12.5 or 125 ng) or saline per side. At the higher dose, NGF blocked STM. In contrast, NGF at dose of 0.5 and 5.0 ng improved LTM. The bFGF infusion at a dose of 125 ng enhanced LTM. However, bFGF did not alter STM. These findings indicate that hippocampal NGF and bFGF modulate STM and LTM in a different manner.


NGF FGF memory consolidation rat 


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  1. 1.
    Atkins, C. M., Selcher, J. J., Petraitis, J. J., Trzaskos, J. M., Sweatt, J. D. 1998The MAPK cascade is required for mammalian associative learningNature Neurosci1602609Google Scholar
  2. 2.
    Baird, A. 1994Fibroblast growth factors: activities and significance of non-neurotrophin neurotrophic growth factorsCurr. Opin. Neurobiol47886Google Scholar
  3. 3.
    Bergado, J. A., Gomez-Soria, A. A., Cruz, R., Fernandez, C. I. 1998Nerve growth factor improves evoked potentials and long-term potentiation in the dentate gyrus of presenile ratsEur. J. Pharmacol345181184Google Scholar
  4. 4.
    Blochl, A., Thoenen, H. 1995Characterization of nerve growth factor (NGF) release from hippocampal neurons: evidence for a constitutive and an unconventional sodium-dependent regulated pathwayEur. J. Neurosci712201228Google Scholar
  5. 5.
    Botta, M., Manetti, F., Corelli, F. 2000Fibroblast growth factors and their inhibitorsCurr. Pharm. Des618971924Google Scholar
  6. 6.
    Eckenstein, F. P. 1994Fibroblast growth factors in the nervous systemJ. Neurobiol2514671480Google Scholar
  7. 7.
    Ginty, D. D., Bonni, A., Greenberg, M. E. 1994NGF activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREBCell77713725Google Scholar
  8. 8.
    Gomez-Pinilla, F., So, V., Kesslak, J. P. 1998Spatial learning and physical activity contribute to the induction of fibroblast growth factor: neural substrates for increased cognition associated with exerciseNeurosci855361Google Scholar
  9. 9.
    Izquierdo, I., da Cunha, C., Rosat, R., Jerusalinsky, D., Ferreira, M. B. C., Medina, J. H. 1992Neurotransmitter receptors involved in memory processing by the amygdala, hippocampus and medial septum of ratsBehav. Neural. Biol581625Google Scholar
  10. 10.
    Izquierdo, I., Quillfeldt, J. A., Zanatta, M. S., Quevedo, J., Schaeffer, E., Schmitz, P. K., Medina, J. H. 1997Sequential role of hippocampus and amygdala, entorhinal cortex and parietal cortex in formation and retrieval of memory for inhibitory avoidance in ratsEur. J.Neurosci9786793Google Scholar
  11. 11.
    Izquierdo, I., Barros, D. M., Mello e Souza, T., Souza, M. M., Izquierdo, L. A., Medina, J. H. 1998Mechanisms for memory types differNature393635636Google Scholar
  12. 12.
    Jerusalinsky, D., Ferreira, M. B. C., Walz, R., da Silva, R. C., Bianchin, M., Ruschel, M. A. C., Zanatta, M. S., Medina, J. H., Izquierdo, I. 1992Amnesia by posttraining infusion of glutamate receptor antagonists into the amygdala, hippocampus, and entorhinal cortexBehav. Neural. Biol587680Google Scholar
  13. 13.
    Kang, H., Schuman, E. M. 1995Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampusScience26716581662Google Scholar
  14. 14.
    Lewin, G. R., and Barde, Y. A. Physiology of the neurotrophins. Annu. Rev. Neurosci 19:289-317Google Scholar
  15. 15.
    Li, A. J., Oomura, Y., Sasaki, K., Suzuki, K., Tooyama, I., Hanai, K., Kimura, H., Hori, T. 1998A single pre-training glucose injection induces memory facilitation in rodents performing various tasks: contribution of acidic fibroblast growth factorNeurosci.85785794Google Scholar
  16. 16.
    Lo, D. 1995Neurotrophic factors and synaptic plasticityNeuron15979981Google Scholar
  17. 17.
    Mistry, S. K., Keefer, E. W., Cunningham, B. A., Edelman, G. M., Crossin, K. L. 2002Cultured rat hippocampal neural progenitors generate spontaneously active neural networksProc. Natl. Acad. Sci.9916211626Google Scholar
  18. 18.
    Nabeshima, T., Ogawa, S., Yamada, K., Ishimaru, H., Fuji, K., Kameyama, T., Fukuta, T., Takeuchi, R., Hayashi, K. 1991Memory impairment and morphological changes in rats after continuous infusion of active fragment of anti-nerve growth factor-antibodyRes. Commun. Chem. Pathol. Pharmacol74141152Google Scholar
  19. 19.
    Oomura, Y., Sasaki, K., Li, A., Yoshii, H., Fukata, Y., Yago, H., Kimura, H., Tooyama, I., Hanai, K., Nomura, Y., Yanaihara, N. 1996Protection against impairment of memory and immunoreactivity in senescence-accelerated mice by acidic fibroblast growth factorAnn. NY. Acad. Sci78633747Google Scholar
  20. 20.
    Paxinos, G., Watson, C. 1996The rat brain in stereotaxic coordinatesAcademic PressSan Diego, CAGoogle Scholar
  21. 21.
    Reuss, B., Bohlen und Halbach, O. 2003Fibroblast growth factors and their receptors in the central nervous systemCell. Tissue. Res313139157Google Scholar
  22. 22.
    Ricceri, L., Alleva, E., Chiarotti, F., Calamandrei, G. 1996Nerve growth factor affects passive avoidance learning and retention in developing miceBrain Res. Bull39219226Google Scholar
  23. 23.
    Roesler, R., Vianna, M., Sant’Anna, M. K., Kuyven, C. R., Kruel, A. V. S., Quevedo, J., Ferreira, M. B. C. 1998Intrahippocampal infusion of the NMDA receptor antagonist AP5 impairs retention of an inhibitory avoidance task: Protection from impairment by pretraining or preexposure to the task apparatusNeurobiol. Learn. Mem698791Google Scholar
  24. 24.
    Sasaki, K., Oomura, Y., Figurov, A., Yagi, H. 1994Acidic fibroblast growth factor facilitates generation of long-term potentiation in rat hippocampal slicesBrain Res. Bull33505511Google Scholar
  25. 25.
    Segal, R. A., Greenberg, M. E. 1996Intracellular signaling pathways activated by neurotrophic factorsAnnu. Rev. Neurosci19463489Google Scholar
  26. 26.
    Sinson, G., Perri, B. R., Trojanowski, J. Q., Flamm, E. S., McIntosh, T. K. 1997Improvement of cognitive deficits and decreased cholinergic neuronal cell loss and apoptotic cell death following neurotrophin infusion after experimental traumatic brain injuryJ. Neurosurg86511518Google Scholar
  27. 27.
    Thoenen, H. 1995Neurotrophins and neuronal plasticityScience270593598Google Scholar
  28. 28.
    Walz, R., Roesler, R., Barros, D. M., Souza, M. M., Rodrigues, C., Sant’Anna, M. K., Quevedo, J., Choi, H. K., Neto, W. P., DeDavide Silva, T. L., Medina, J. H., Izquierdo, I. 1999Effects of posttraining infusions of a mitogen-activated protein kinase kinase inhibitor into hippocampus or entorhinal cortex on the short- and long-term inhibitory avoidance retentionBehav. Pharmacol10723730Google Scholar
  29. 29.
    Walz, R., Roesler, R., Quevedo, J., Madruga, M., Rodrigues, C., Godfried, C., Medina, J. H., Izquierdo, I. 1999Time-dependent impairment of inhibitory avoidance retention by mitogen activated protein kinase kinase inhibitor infusion into the cortical and limbic structuresNeurobiol. Learn. Mem731120Google Scholar
  30. 30.
    Walz, R., Lenz, G., Roesler, R., Vianna, M. M., Martins, V., Brentani, R., Rodnight, R., Izquierdo, I. 2000Time-dependent enhancement of inhibitory avoidance retention and MAPK activation by post-training infusion of nerve growth factor into CA1 region of hippocampus of adult ratsEur. J. Neurosci1221852189Google Scholar
  31. 31.
    Woolf, N. J., Milov, A. M., Schweitzer, E. S., Roghani, A. 2001Elevation of nerve growth factor and antisense knockdown of TrkA receptor during contextual memory consolidationJ. Neurosci2110471055Google Scholar
  32. 32.
    Xing, J., Kornhauser, J. M., Xia, Z., Thiele, E. A., Greenberg, M. E. 1998Nerve growth factor activates extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways to stimulate CREB serine 133 phosphorylationMol. Cell. Biol1819461955Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Roger Walz
    • 1
  • Rafael Roesler
    • 2
  • Adalisa Reinke
    • 3
  • Márcio Rodrigo Martins
    • 3
  • João Quevedo
    • 3
    • 4
    Email author
  • Ivan Izquierdo
    • 4
  1. 1.Departamento de MedicinaUniversidade do Vale do ItajaíItajaíBrazil
  2. 2.Laboratório de Neurofarmacologia Pré-Clínica, Departamento de FarmacologiaInstituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do SulPorta AlegreBrazil
  3. 3.Laboratório de NeurociênciasUniversidade do Extremo Sul CatarinenseCriciúmaBrazil
  4. 4.Centro de Memória, Departamento de BioquímicaInstituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do SulPorto AlegreBrazil

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