Metabolic Brain Disease

, Volume 20, Issue 1, pp 73–80

Chronic Hyperprolinemia Provokes a Memory Deficit in the Morris Water Maze Task

  • Caren Serra Bavaresco
  • Emílio Luíz Streck
  • Carlos Alexandre Netto
  • Angela Terezinha Souza de Wyse


In the present study we investigated the effect of chronic proline (Pro) administration on rat performance in the Morris water maze task. Rats received s.c. injections of Pro twice a day at 8 h intervals from the 6th to the 28th days of age and equivalent volume of 0.9% saline solution (control). On the 60th day of life, rats were subjected to the water maze task. Results showed that chronic Pro administration provokes impairment on spatial learning, as shown by the increase of latency in acquisition and retention and by a reduced efficiency to find the platform position in the working memory test. Present results suggest that hyperprolininemia causes cognitive dysfunction and might be relevant to explain, at least in part, the neurological dysfunction associated with hyperprolinemia.


Hyperprolinemia type II proline memory water maze rats 


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  1. Ault, B., and Nadler, J.V. (1984). Evidence that L-proline selectively depolarizes pyramidal cells in the rat hippocampal slices. Soc. Neurosci. Abstr. 10:229.Google Scholar
  2. Ault, B., Wang, T.R., and Means, E.D. (1987). L-Proline depolarizes rat spinal motoneurons by excitatory amino acid-sensitive mechanism. Br. J. Pharmacol. 92:319–326.PubMedGoogle Scholar
  3. Cherkin, A., Eckardt, M.J., and Gerbrandt, L.K. (1976). Memory: Proline induces retrograde amnesia in chicks. Science 193:242–244.PubMedGoogle Scholar
  4. Cohen, S.M., and Nadler, J.V. (1997). Proline-induced potentiation of glutamate transmission. Brain Res. 761:271–282.CrossRefPubMedGoogle Scholar
  5. Davis, P.H., and Squire, L.R. (1984). Protein synthesis and memory: A review. Psychol. Bull. 96:518–559.CrossRefPubMedGoogle Scholar
  6. Delwing, D., Bavaresco, C.S., Wannmacher, C.D., Wajner, M., Dutra-Filho, C.S., and Wyse, A.T.S. (2002). Proline induces oxidative stress in cerebral cortex of rats. Int. J. Dev. Neurosci. 760:1–6.Google Scholar
  7. Delwing, D., Chiarani, F., Delwing, D., Bavaresco, C.S., Wannmacher, C.D., Wajner, M., and Wyse, A.T.S. (2003). Proline reduces acetylcholinesterase activity in cerebral cortex of rats. Metab. Brain Dis. 18:79–86.CrossRefPubMedGoogle Scholar
  8. D’Hooge, R.D., and De Deyn, P.P. (2001). Aplications of the Morris water maze in the study of learning and memory. Brain Res. Rev. 36:60–90.CrossRefPubMedGoogle Scholar
  9. Franzon, R., Lamers, M.L., Stefanello, F.M., Wannmacher, C.M.D., Wajner, M., and Wyse, A.T.S. (2003). Evidence that oxidative stress is involved in the inhibitory effect of proline on Na+,K+-ATPase activity in synaptic plasma membrane of rat hippocampus. Int. J. Dev. Neurosci. 21:303–307.CrossRefPubMedGoogle Scholar
  10. Fremeau, R.T., Caron, M.G., and Blakely, R.D. (1992). Molecular cloning and expression of a high affinity L-proline transporter expressed in putative glutamatergic pathways of rats brain. Neuron 8:915–926.CrossRefPubMedGoogle Scholar
  11. Fremeau, R.T., Velaz-Faircloth, M., Miller, J.W., Henzi, V.A., Cohen, S.M., Nadler, J.A., Shafqat, S., Blakely, R.D., and Domin, B. (1996). A novel nonopioid action of enkephalins: Competitive inhibitor of the mammalian brain high affinity L-proline transporter. Mol. Pharmacol. 49:1033–1041.PubMedGoogle Scholar
  12. Halliwell, B. (1996). Free radicals, protein and DNA: Oxidative damage versus redox regulation. Trends Neurosci. 8:22–26.CrossRefGoogle Scholar
  13. Henzi, V., Reichiling, D.B., Helm, S.M., and MacDermott, A.B. (1992). L-Proline activates glutamate and glycine receptores in cultured rat dorsal horn neurones. Mol. Pharmacol. 41:793–801.PubMedGoogle Scholar
  14. Johnson, J.I., and Roberts, E. (1984). Proline, glutamate and glutamine metabolism in mouse brain synaptossomes. Brain Res. 323:247–256.CrossRefPubMedGoogle Scholar
  15. Loo, Y.H., Fulton, A., Miller, K., and Wisniewski, M.H. (1980). Phenylacetate effects in synaptic development. Life Sci. 27:1280–1289.Google Scholar
  16. Martin, D., Ault, B., and Nadler, J.V. (1992). NMDA receptor-mediated depolarizing action of proline on CA1 pyramidal cells. Eur. J. Pharmacol. 219:59–66.CrossRefPubMedGoogle Scholar
  17. Moreira, J.C.F., Wannmacher, C.D., Costa, S.M., and Wajner, M. (1989). Effect of proline administration on rat behavior in aversive and nonaversive tasks. Pharmacol. Biochem. Biohav. 32:885–890.CrossRefGoogle Scholar
  18. Morris, R.G.M., Garrud, J.N.P., and Rawlins, J.O. (1982). Place navigation impaired in rats with hippocampal lesions. Nature 297:681–683.CrossRefPubMedGoogle Scholar
  19. Munoz, M.D., Monfort, P., Gaztelu, J.M., and Felipo, V. (2000). Hyperammonemia impairs NMDA receptor-dependent long-term potentiation in the CA1 of rat hippocampus in vitro. Neurochem. Res. 25:437–441.CrossRefPubMedGoogle Scholar
  20. Nadler, J.V., Wang, A., and Hakim, A. (1988). Toxicity of L-proline toward rat hippocampal neurons. Brain Res. 456:168–172.CrossRefPubMedGoogle Scholar
  21. Netto, C.A., Hodges, H., Sinden, J.D., LePeillet, E., Kershaw, T., Sowinski, P., Meldrum, B.S., and Gray, J.A. (1993). Foetal grafts from hippocampal region superior alleviate ischaemic-induced behavioral deficits. Behav. Brain Res. 58:107–112.CrossRefPubMedGoogle Scholar
  22. Pace, J.R., Martin, B.M., Paul, S.M., and Rowski, A. (1992). High concentrations of neutral amino acids activates NMDA receptor currents in rat hippocampal neurons. Neurosci. Lett. 141:97–100.CrossRefPubMedGoogle Scholar
  23. Phang, J.M., Hu, C.A., and Valle, D. (2001). Disorders of proline and hydroxyproline metabolism. In (C.R. Scriver, A.I. Beaudet, W.S. Sly, and D.Valle, eds.), The Metabolic and Molecular Bases of Inherited Disease, 8th edn., McGraw-Hill, New York, pp. 1821–1838.Google Scholar
  24. Pontes, Z.L., Oliveira, L.S., Bavaresco, C.S., Streck, E.L., Dutra-Filho, C.S., Wajner, M., Wannmacher, C.M., and Wyse, A.T.S. (1999). Proline administration decreases Na+,K+-ATPase activity in the synaptic plasma membrane from cerebral cortex of rats. Metab. Brain Dis. 14:265–272.CrossRefPubMedGoogle Scholar
  25. Pontes, Z.L., Oliveira, L.S., Franzon, R., Wajner, M., Wannmacher, C.D., and Wyse, A.T.S. (2001). Inhibition of Na+,K+-ATPase activity from rat hippocampus by proline. Neurochem. Res. 26:1321–1326.CrossRefPubMedGoogle Scholar
  26. Socci, D.J., Crandall, B.M., and Arendash, G.W. (1995). Chronic antioxidant treatment improves the cognitive performance of aged rats. Brain Res. 693:88–94.CrossRefPubMedGoogle Scholar
  27. Van Harreveld, A., and Fifkova, E. (1974). Involvement of glutamate in memory formation. Brain Res. 13:455–467.CrossRefGoogle Scholar
  28. Velaz-Faircloth, M., Guadano-Ferraz, A., Henzi, V.A., and Fremeau, R.T. (1995). Mammalian brain-specific L-proline transporter. Neuronal localization of mRNA and enrichment of transporter protein in synaptic plasma membranes. J. Biol. Chem. 270:15755–15761.CrossRefPubMedGoogle Scholar
  29. Warren, S.G., and Juraska, J.M. (2000). Sex differences and phase effects on water maze performance in aged rats. Neurobiol. Learn. Mem. 74:229–240.CrossRefPubMedGoogle Scholar
  30. Youssef, F.F., and Addae, J.I. (2002). Learning may provide neuroprotection against dementia. West. Ind. Med. J. 51:143–147.Google Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Caren Serra Bavaresco
    • 1
  • Emílio Luíz Streck
    • 1
  • Carlos Alexandre Netto
    • 1
  • Angela Terezinha Souza de Wyse
    • 1
    • 2
  1. 1.Department of BiochemistryICBS, Universidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Departamento de BioquímicaICBS, Universidade Federal do Rio Grande do SulPorto AlegreBrazil

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