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Impairment of cerebral glucose metabolism parallels learning and memory dysfunctions after intracerebral streptozotocin

  • R. Nitsch
  • G. Mayer
  • R. Galmbacher
  • G. Galmbacher
  • V. Apell
  • S. Hoyer
Part of the Key Topics in Brain Research book series (KEYTOPICS)

Summary

In early-onset Alzheimer’s disease, the cerebral glucose metabolism is disturbed in a characteristic manner. Here, we attempted to mimick these alterations by intracerebral injection of the pancreatic islet cell toxin streptozotocin (STZ) into the rat brain ventricles. This treatment resulted in a reduced arteriovenous difference (AVD) of glucose, an increased AVD of lactate, whereas the AVDs of oxygen and carbon dioxide remained unchanged. In addition, learning and memory functions were impaired. These alterations may be related to a disturbance of the local action of insulin on the brain. Furthermore, the approach reported here may provide a model for the study of the early pathogenetic events of Alzheimer’s disease.

Keywords

Cerebral Glucose Metabolism Passive Avoidance Test Pancreatic Endocrine Cell Sensory Attention Cognitive Attention 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Alpert S, Hanahan D, Teitelman G (1988) Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. Cell 53: 295–308PubMedCrossRefGoogle Scholar
  2. Baskin DG, Figlewicz DP, Woods SC, Porte D, Dorsa DM (1987) Insulin in the brain. Ann Rev Physiol 49: 335–347CrossRefGoogle Scholar
  3. Bolaffi JL, Nagamatsu S, Harris J, Grodsky GM (1987) Protection by thymidine, an inhibitor of polyadenosine diphosphate ribosylation, of streptozotocin inhibition of insulin secretion. Endocrinology 120: 2117–2122PubMedCrossRefGoogle Scholar
  4. Boyd FT, Clarke DW, Muther TF, Raizada MK (1985) Insulin receptors and insulin modulation of norepinephrine uptake in neuronal cultures from rat brain. J Biol Chem 260: 15880–15884PubMedGoogle Scholar
  5. Clarke DW, Mudd L, Boyd FT, Fields M, Raizada MK (1986) Insulin is released from rat brain neuronal cells in culture. J Neurochem 47: 831–836PubMedCrossRefGoogle Scholar
  6. Corp ES, Woods SC, Porte D, Dorsa DM, Figlewicz DP, Baskin DG (1986) Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography. Neurosci Lett 70: 17–22PubMedCrossRefGoogle Scholar
  7. Danguir J, Nicolaidis S (1984) Chronic cerebroventricular infusion of insulin causes selective increase of slow wave sleep in rats. Brain Res 306: 97–103PubMedCrossRefGoogle Scholar
  8. Fram RJ, Marinus MG, Volkert MR (1988) Gene expression in E. coli after treatment with streptozotocin. Mutat Res 198: 45–51PubMedCrossRefGoogle Scholar
  9. Havrankova J, Roth J, Brownstein M (1978) Insulin receptors are widely distributed in the central nervous system of the rat. Nature 272: 827–829PubMedCrossRefGoogle Scholar
  10. Hill JM, Lesniak MA, Pert CB, Roth J (1986) Autoradiographic localization of insulin receptors in rat brain: prominence in olfactory and limbic areas. Neuroscience 17: 1127–1138PubMedCrossRefGoogle Scholar
  11. Hoyer S, Nitsch R (1989) Cerebral excess release of neurotransmitter amino acids subsequent to reduced cerebral glucose metabolism in early-onset dementia of Alzheimer type. J Neural Transm 75: 227–232PubMedCrossRefGoogle Scholar
  12. Hoyer S, Oesterreich K, Wagner O (1988) Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type? J Neurol 235: 143–148PubMedCrossRefGoogle Scholar
  13. Hussin AH, Skett P (1988) Lack of effect of insulin in hepatocytes isolated from streptozotocin-diabetic male rats. Biochem Pharmacol 37: 1683–1689PubMedCrossRefGoogle Scholar
  14. Junod A, Lambert AE, Stauffacher W, Renold AE (1969) Diabetogenic action of streptozotocin: relationship of dose to metabolic response. J Clin Invest 48: 2119–2139CrossRefGoogle Scholar
  15. Kadowaki T, Kasuga M, Akanuma Y, Ezaki O, Takaku F (1984) Decreased autophosphorylation of the insulin receptor-kinase in streptozotocin diabetic rats. J Biol Chem 259: 14208–14216PubMedGoogle Scholar
  16. Kolb-Bachofen V, Epstein S, Kiesel U, Kolb H (1988) Low-dose streptozotocininduced diabetes in mice. Diabetes 37: 21–27PubMedCrossRefGoogle Scholar
  17. Kyriakis JM, Hausman RE, Peterson SW (1987) Insulin stimulates choline acetyltransferase activity in cultured embryonic chicken retina neurons. Proc Natl Acad Sci USA 84: 7463–7467PubMedCrossRefGoogle Scholar
  18. Mayer G, Nemeth G, Hoyer S (1988) Psychometric altersabhängiger Aufinerksamkeitsveränderungen — Darstellung an der Ratte. Z Gerontol 21: 87–92PubMedGoogle Scholar
  19. Nemeth G, Mayer G, Hoyer S (1989) A new psychometric test of attention-related behaviour in rats; its validity in the aging process. Arch Gerontol Geriatr 8: 29–36PubMedCrossRefGoogle Scholar
  20. Palovcik RA, Phillips MI, Kappy MS, Raizada MK (1984) Insulin inhibits pyramidal neurons in hippocampal slices. Brain Res 309: 187–191PubMedCrossRefGoogle Scholar
  21. Pellegrino DA, Miletich DJ, Albrecht RF (1987) Effects of superfused insulin on cerebral cortical glucose utilization in awake goats. Am J Physiol 253 (Endocrinol Metab 16): E418 - E427Google Scholar
  22. Phillips ME, Coxon RV (1976) Effect of insulin and phenobarbital on uptake of 2-deoxyglucose by brain slices and hemidiaphragms. J Neurochem 27: 643–645PubMedCrossRefGoogle Scholar
  23. Rinaudo MT, Curto M, Bruno R (1985) Effect of insulin on the pyruvate dehydrogenase complex in the rat brain. Ital J Biochem 34: 229–238PubMedGoogle Scholar
  24. Rosen OM (1987) After insulin binds. Science 237: 1452–1458PubMedCrossRefGoogle Scholar
  25. Sakaguchi T, Bray GA (1987) Intrahypothalamic injection of insulin decreases firing rate of sympathetic nerves. Proc Natl Acad Sci USA 84: 2012–2014PubMedCrossRefGoogle Scholar
  26. Sauter A, Goldstein M, Engel J, Keta K (1983) Effect of insulin on central catecholamines. Brain Res 260: 330–333PubMedCrossRefGoogle Scholar
  27. Schechter R, Holtzclaw L, Sadiq F, Kahn A, Devaskar S (1988) Insulin synthesis by isolated rabbit neurons. Endocrinology 123: 505–513PubMedCrossRefGoogle Scholar
  28. Smit AB, Vreugdenhil E, Ebberink RHM, Geraerts WPH, Klootwijk J, Joosse J (1988) Growth-controlling molluscan neurons produce the precursor of an insulin-related peptide. Nature 331: 535–538PubMedCrossRefGoogle Scholar
  29. Steinfelder HJ, Joost HG (1988) Inhibition of insulin-stimulated glucose transport in rat adipocytes by nucleoside transport inhibitors. Febs Lett 227: 215–219PubMedCrossRefGoogle Scholar
  30. Werther GA, Hogg A, Oldfield BJ, McKinley MJ, Fidor R, Allen AM, Mendelsohn FOK (1987) Localization and characterization of insulin receptors in rat brain and pituitary gland using in vitro autoradiography and computerized densitometry. Endocrinology 121: 1562–1570PubMedCrossRefGoogle Scholar
  31. Woods SC, Lotter EC, McKay LD, Ponte D Jr (1979) Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 282: 503–505PubMedCrossRefGoogle Scholar
  32. Yorek MA, Dunlap JA, Ginsberg BH (1987) Amino acid and putative neurotransmitter transport in human Y79 retinoblastoma cells. J Biol Chem 262: 10968–10993Google Scholar
  33. Young WS (1986) Periventricular hypothalamic cells in the rat brain contain insulin mRNA. Neuropeptides 9: 93–97CrossRefGoogle Scholar
  34. Zucker PF, Archer MC (1988) Streptozotocin toxicity to cultured pancreatic islets of the Syrian hamster. Cell Biol Toxicol 4: 349–357PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1990

Authors and Affiliations

  • R. Nitsch
    • 1
  • G. Mayer
    • 1
  • R. Galmbacher
    • 1
  • G. Galmbacher
    • 1
  • V. Apell
    • 1
  • S. Hoyer
    • 1
  1. 1.Department of Pathochemistry and General NeurochemistryUniversity of HeidelbergHeidelbergFederal Republic of Germany

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