Skip to main content

Advertisement

Log in

Studies of the effects of fragment (25–35) of beta-amyloid peptide on the behavior of rats in a radial maze

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Abstract

Decreases in cognitive functions, particularly long-term (episodic) and working memory, are among the earliest prognostic signs of Alzheimer’s disease. The toxicity of β-amyloid peptide is regarded as a major cause of neurodegeneration and cognitive impairment in this disease. The present report describes studies of the effects of intracerebroventricular administration of β-amyloid peptide (25–35) (Aβ(25–35)) on the reproduction of a previously assimilated habit consisting of finding food in an eight-arm radial maze in rats. Aβ (25–35) was given bilaterally at doses of 15 and 30 nmol/animal seven days after preliminary training. Testing was performed 60 days after peptide administration. The results showed that Aβ(25–35) impaired working memory in rats without having any significant effect on the retention of responses. We were unable to demonstrate any relationship between memory impairment and the dose of peptide given. These data provide evidence of the ability of Aβ(25–35) to produce greater degradation of working memory function than long-term memory function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. O. S. Mitrokhina, M. Yu. Stepanichev, N. A. Lazareva, et al., “The effects of intracerebroventricular administration of fragment (25–35) of beta-amyloid peptide on the level of lipid peroxidation in rat brain structures and blood,” Dokl. Ros. Akad. Nauk., 368, No.5, 711–713 (1999).

    Google Scholar 

  2. M. Yu. Stepanichev, N. A. Lazareva, M. V. Onufriev, et al., “The effects of administration of fragment (25–35) of beta-amyloid peptide on behavior in rats,” Zh. Vyssh. Nerv. Deyat., 47, No.3, 597–600 (1997).

    Google Scholar 

  3. M. Yu. Stepanichev, Yu. V. Moiseeva, and N. V. Gulyaeva, “‘Injection’ models of Alzheimer’s disease: oxidative stress in the mechanism of toxicity AF64A and β-amyloid peptide in rodents,” Neirokhimiya, 19, No.3, 165–175 (2002).

    Google Scholar 

  4. M. Yu. Stepanichev, M. V. Onufriev, O. S. Mitrokhina, et al., “Neurochemical, behavioral, and neuromorphological effects of central administration of beta-amyloid peptide (25–35) in rats,” Neirokhimiya, 17, No.4, 291–306 (2000).

    Google Scholar 

  5. V. V. Trubetskaya, M. Yu. Stepanichev, M. V. Onufriev, et al., “Administration of aggregated beta-amyloid peptide (25–35) induces changes in long-term potentiation in the hippocampus in vivo,” Zh. Vyssh. Nerv. Deyat., 51, No.6, 701–704 (2001).

    Google Scholar 

  6. E. Abe, F. Casamenti, L. Giovannelli, et al., “Administration of amyloid beta-peptides into the medial septum of rats decreases acetylcholine release from hippocampus in vivo,” Brain Res., 636, 162–164 (1994).

    Google Scholar 

  7. A. Baddeley, “The fractionation of working memory,” Proc. Natl. Acad. Sci. USA, 93, 13468–13472 (1993).

    Google Scholar 

  8. G. T. Bartoo, D. Nochlin, D. Chang, et al., “The mean Aβ load in the hippocampus correlates with duration and severity of dementia in subgroups of Alzheimer disease,” J. Neuropathol. Exp. Neurol., 56, 531–540 (1997).

    Google Scholar 

  9. S. Y. Chen, J. W. Wright, and C. D. Barnes, “The neurochemical and behavioral effects of beta-amyloid peptide (25–35),” Brain Res., 720, 54–60 (1996).

    Google Scholar 

  10. J. J. Chrobak, I. Hanin, D. E. Schmechel, and T. J. Walsh, “AF64A-induced working memory impairment: behavioral, neurochemical and histological correlates,” Brain Res., 463, 107–117 (1988).

    Google Scholar 

  11. R. F. Cowburn, B. Wiehager, E. Trief, et al., “Effects of β-amyloid-(25–35) peptides on radioligand binding to excitatory amino acid receptors and voltage-dependent calcium channels: evidence for a selective affinity for glutamate and glycine recognition sites of the NMDA receptor,” Neurochem. Res., 22, 1437–1442 (1997).

    Google Scholar 

  12. W. K. Cullen, Y.-H. Suh, R. Anwyl, and M. J. Rowan, “Block of LTP in rat hippocampus in vivo by β-amyloid precursor protein fragments,” Neuroreport, 8, 3213–3217 (1997).

    Google Scholar 

  13. S. Delobette, A. Privat, and T. Maurice, “In vitro aggregation facilitates beta-amyloid peptide-(25–35)-induced amnesia in the rat,” Eur. J. Pharmacol., 319, 1–4 (1997).

    Google Scholar 

  14. D. W. Dickson, H. A. Crystal, L. A. Mattiace, et al., “Identification of normal and pathological aging in prospectively studied nondemented elderly humans,” Neurobiol. Aging, 13, 179–189 (1992).

    Google Scholar 

  15. L. Giovanelli, F. Casamenti, C. Scali, et al., “Differential effects of amyloid peptides β-(1–40) and β-(25–35) injections into the rat nucleus basalis,” Neurosci., 66, 781–792 (1995).

    Google Scholar 

  16. N. V. Gulyaeva, I. V. Victorov, M. Yu. Stepanichev, et al., “Intracerebroventricular administration of beta-amyloid peptide (25–35) induces oxidative stress and neurodegeneration in rat brain,” in: Progress in Alzheimer’s and Parkinson’s Diseases, A. Fisher et al. (eds.) Plenum Press, New York (1998), pp. 89–98.

    Google Scholar 

  17. T. Harkany, J. Mulder, M. Sasvan, et al, “N-methyl-D-aspartate receptor antagonist MK-801 and radical scavengers protect cholinergic nucleus basalis neurons against β-amyloid neurotoxicity,” Neurobiol. Dis., 6, 109–121 (1999).

    Google Scholar 

  18. K. Hsiao, P. Chapman, S. Nilsen, et al., “Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice,” Science, 274, 99–102 (1996).

    Google Scholar 

  19. R. Katzman, R. Terry, R. DeTeresa, et al., “Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques,” Ann. Neurol., 23, 138–144 (1988).

    Google Scholar 

  20. H. Lin, R. Bhatia, and R. Lal, “Amyloid (beta) protein forms ion channels: implications for Alzheimer’s disease pathophysiology,” FASEB J., 15, 2433–2444 (2001).

    Google Scholar 

  21. Y. Luo, D. B. Hawyer, K. Iwasaki, et al., “Physiological levels of β-amyloid peptide stimulate protein kinase C in PC12 cells,” Brain Res., 769, 287–295 (1997).

    Google Scholar 

  22. M. P. Mattson, “Modification of ion homeostasis by lipid peroxidation: roles in neuronal degeneration and adaptive plasticity,” Trends Neurosci., 21, 53–57 (1998).

    Google Scholar 

  23. M. P. Mattson, S. W. Barger, B. Cheng, et al., “β-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer’s disease,” Trends. Neurosci., 16, 409–414 (1993).

    Google Scholar 

  24. T. Maurice, B. P. Lockart, and A. Privat, “Amnesia induced in mice by centrally administered beta-amyloid peptides involves cholinergic dysfunction,” Brain Res., 706, 181–193 (1996).

    Google Scholar 

  25. M. P. McDonald, E. E. Dahl, Y. B. Overmeier, et al., “Effects of an exogenous β-amyloid peptide on retention for spatial learning,” Behav. Neural. Biol., 62, 60–67 (1994).

    Google Scholar 

  26. M. P. McDonald, E. E. Dahl, Y. B. Overmeier, et al., “Reversal of β-amyloid-induced retention deficit after exposure to training and state cues,” Neurobiol. Learn. Mem., 65, 35–47 (1996).

    Google Scholar 

  27. M. P. McDonald and Y. B. Overmeier, “Present imperfect: a critical review of animal models of mnemonic impairments in Alzheimer’s disease,” Neurosci. Biobehav. Rev., 22, 99–120 (1998).

    Google Scholar 

  28. R. G. M. Morris, “Episodic-like memory in animals: psychological criteria, neural mechanisms and the value of episodic-like tasks to investigate animal models of neurodegenerative disease,” Phil. Trans. Roy. Soc. Lond., 356, 1453–1463 (2001).

    Google Scholar 

  29. J. Naslund, V. Haroutunian, R. Mohs, et al., “Correlation between levels of amyloid beta-peptide in the brain and cognitive decline,” J. Amer. Med. Assoc., 283, 1571–1577 (2000).

    Google Scholar 

  30. A. Nitta, A. Itoh, T. Hasegawa, and T. Nabeshima, “β-amyloid protein-induced Alzheimer’s disease animal model,” Neurosci. Lett., 289, 63–66 (1994).

    Google Scholar 

  31. A. Olariu, M. H. Tran, K. Yamada, et al., “Memory deficits and increased emotionality induced by beta-amyloid (25–35) are correlated with the reduced acetylcholine release and altered phorbol dibutyrate binding in the hippocampus,” J. Neural Transm., 108, 1065–1079 (2001).

    Google Scholar 

  32. D. S. Olton, “Spatial memory,” Sci. Amer., 236, 82–98 (1977).

    Google Scholar 

  33. S. O’Mahony, T. Harkany, A. A. M. Rensink, et al., “β-amyloid-induced cholinergic denervation correlates with enhanced nitric oxide synthase activity in rat cerebral cortex: Reversal by NMDA receptor blockade,” Brain Res. Bull., 45, 405–411 (1998).

    Google Scholar 

  34. G. Paxinos and C. Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press, Sidney (1982).

    Google Scholar 

  35. C. J. Pike, D. Brudick, A. J. Walencevicz, et al., “Neurodegeneration induced by β-amyloid peptides in vitro: the role of peptide assembly state,” J. Neurosci., 13, 1676–1687 (1993).

    Google Scholar 

  36. D. J. Selkoe, “Alzheimer’s disease: genes, proteins, and therapy,” Physiol. Rev., 81, 741–766 (2001).

    Google Scholar 

  37. A. Stephan, S. Laroche, and S. Davis, “Generation of aggregated β-amyloid in the rat hippocampus impairs synaptic transmission and plasticity and causes memory deficits,” J. Neurosci., 21, 5703–5714 (2001).

    Google Scholar 

  38. W. Sweeney, J. Luedtke, M. P. McDonald, and J. B. Overmeier, “Intrahippocampal β-amyloid impairs win-shift radial maze performance in rats,” Neurobiol. Learn. Mem., 68, 97–101 (1997).

    Google Scholar 

  39. J. P. Terranova, J. P. Kan, J. J. Storme, et al., “Administration of amyloid beta-peptides in the rat medial septum causes memory deficits: reversal by SR 57746A, a non-peptide neurotrophic compound,” Neurosci. Lett., 213, 79–82 (1996).

    Google Scholar 

  40. L. Tong, P. L. Thornton, R. Balazs, and C. W. Cotman, “β-Amyloid-(1–42) impairs activity-dependent cAMP-response element-binding protein signalling in neurons at concentrations in which cell survival is not compromised,” J. Biol. Chem., 276, 17301–17306 (2001).

    Google Scholar 

  41. M. H. Tran, K. Yamada, A. Olariu, et al., “Amyloid β-peptide induces nitric oxide production in rat hippocampus: association with cholinergic dysfunction and amelioration by inducible nitric oxide synthase inhibitors,” FASEB J., 15, 1407–1409 (2001).

    Google Scholar 

  42. M. A. Westerman, D. Cooper-Blacketer, A. Mariash, et al., “The relationship between Aβ and memory in the Tg2576 mouse model of Alzheimer’s disease,” J. Neurosci., 22, 1858–1867 (2002).

    Google Scholar 

  43. Y. Yamaguchi and S. Kawashima, “Effects of amyloid-β-(25–35) on passive avoidance, radial-arm maze learning and choline acetyltransferase activity in the rat,” Eur. J. Pharmacol., 412, 265–272 (2001).

    Google Scholar 

  44. B. A. Yankner, L. K. Duffy, and D. A. Kirschner, “Neurotrophic and neurotoxic effects of amyloid β protein: reversal by tachykinin neuropeptides,” Science, 250, 279–282 (1990).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti, Vol. 54, No. 3, pp. 382–389, May–June, 2004.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stepanichev, M.Y., Moiseeva, Y.V., Lazareva, N.A. et al. Studies of the effects of fragment (25–35) of beta-amyloid peptide on the behavior of rats in a radial maze. Neurosci Behav Physiol 35, 511–518 (2005). https://doi.org/10.1007/s11055-005-0086-1

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-005-0086-1

Key words

Navigation