Skip to main content
SpringerLink
Log in

Experimental Approach to Alzheimer Disease

  • Reference work entry
  • First Online:
Handbook of Neurotoxicity

  • 2781 Accesses

Abstract

This review on current experimental models of Alzheimer disease is based on human postmortem findings showing keystone markers for a pathology within the ß-amyloid transduction cascade as well as pathology in the mechanism of phosphorylation of τau protein. Evidence for risk factors triggering this devastating disease focuses on type II diabetes. Therefore, modelling Alzheimer disease tries to get profound knowledge of these underlying mechanisms by studying experimental animal models. Here will be discussed in detail two pharmacological models, the one mirroring type II diabetes-induced AD pathology by streptozotocin and its influences on the insulin/insulin receptor cascade as well as ß-amyloid and τau pathologies. Behavioral studies give evidence that this model is currently the most detailed described AD model. While transgenic mouse models, like the APP Tg2576 model, demonstrate ß-amyloid plaque formation and impaired memory rather in old age, streptozotocin is able to aggravate the process of pathology so that AD pathology is seen months earlier. This indicates a profound interaction of AD pathology with the insulin/insulin receptor cascade and pathobiochemistry.

Modelling cholinergic deficits has been done by using the cholinotoxin AF64A. This model reflects changes in the acetylcholine metabolism as well as in monoaminergic transmitter systems, and behavioral studies are in line with AD-based impairment of learning and memory. However, ß-amyloid and τau pathologies as well as insulin-resistant brain state have not been studied in detail.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 549.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Agrawal, R., Tyagi, E., Shukla, R., & Nath, C. (2011). Insulin receptor signaling in rat hippocampus: A study in STZ (ICV) induced memory deficit model. European Neuropsychopharmacology, 21, 261–273.

    CAS  PubMed  Google Scholar 

  • Arluison, M., Quignon, M., Thorens, B., Leloup, C., & Penicaud, L. (2004a). Immunocytochemical localization of the glucose transporter 2 (GLUT2) in the adult rat brain. II. Electron microscopic study. Journal of Chemical Neuroanatomy, 28, 137–146.

    CAS  PubMed  Google Scholar 

  • Arluison, M., Quignon, M., Nguyen, P., Thorens, B., Leloup, C., & Penicaud, L. (2004b). Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain–an immunohistochemical study. Journal of Chemical Neuroanatomy, 28, 117–136.

    CAS  PubMed  Google Scholar 

  • Ashe, K. H. (2001). Learning and memory in transgenic mice modeling Alzheimer’s disease. Learning and Memory, 8, 301–308.

    CAS  PubMed  Google Scholar 

  • Ayala-Grosso, C. A., & Urbina-Paez, R. (1999). Septohippocampal adaptive GABAergic responses by AF64A treatment. Journal of Neuroscience Research, 55, 178–186.

    CAS  PubMed  Google Scholar 

  • Bennett, D. A., Cochran, E. J., Saper, C. B., Leverenz, J. B., Gilley, D. W., & Wilson, R. S. (1993). Pathological changes in frontal cortex from biopsy to autopsy in Alzheimer’s disease. Neurobiology of Aging, 14, 589–596.

    CAS  PubMed  Google Scholar 

  • Blennow, K., de Leon, M., & Zetterberg, H. (2006). Alzheimer’s disease. The Lancet, 368, 387–403.

    CAS  Google Scholar 

  • Blokland, A., & Jolles, J. (1993). Spatial learning deficit and reduced hippocampal ChAT activity in rats after an ICV injection of streptozotocin. Pharmacology Biochemistry and Behavior, 44, 491–494.

    CAS  Google Scholar 

  • Blokland, A., & Jolles, J. (1994). Behavioral and biochemical effects of an ICV injection of streptozotocin in old Lewis rats. Pharmacology Biochemistry and Behavior, 47, 833–837.

    CAS  Google Scholar 

  • Blondel, O., & Portha, B. (1989). Early appearance of in vivo insulin resistance in adult streptozotocin-injected rats. Diabète & Métabolisme, 15, 382–387.

    CAS  Google Scholar 

  • Brant, A. M., Jess, T. J., Milligan, G., Brown, C. M., & Gould, G. W. (1993). Immunological analysis of glucose transporters expressed in different regions of the rat brain and central nervous system. Biochemical and Biophysical Research Communications, 192, 1297–1302.

    CAS  PubMed  Google Scholar 

  • Cole, G. M., & Frautschy, S. A. (2007). The role of insulin and neurotrophic factor signaling in brain aging and Alzheimer’s disease. Experimental Gerontology, 42, 10–21.

    CAS  PubMed  Google Scholar 

  • Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science, 261, 921–923.

    CAS  PubMed  Google Scholar 

  • Correia, S. C., Santos, R. X., Perry, G., Zhu, X., Moreira, P. I., & Smith, M. A. (2011). Insulin-resistant brain state: The culprit in sporadic Alzheimer’s disease? Ageing Research Reviews, 10, 264–273.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995). Inhibition of glycogen synthase kinase-3 by insulin mediated protein kinase. Nature, 378, 785–789.

    CAS  PubMed  Google Scholar 

  • Crystal, H., Dickson, D., Fuld, P., Masur, D., Scott, R., Mehler, M., Masdeu, J., Kawas, C., Aronson, M., & Wolfson, L. (1988). Clinico-pathologic studies in dementia: Nondemented subjects with pathologically confirmed Alzheimer’s disease. Neurology, 38, 1682–1687.

    CAS  PubMed  Google Scholar 

  • Davies, C. A., Mann, D. M., Sumpter, P. Q., & Yates, P. O. (1987). A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer’s disease. Journal of the Neurological Sciences, 78, 151–164.

    CAS  PubMed  Google Scholar 

  • Davis, D. G., Schmitt, F. A., Wekstein, D. R., & Markesbery, W. R. (1999). Alzheimer neuropathologic alterations in aged cognitively normal subjects. Journal of Neuropathology and Experimental Neurology, 58, 376–388.

    CAS  PubMed  Google Scholar 

  • de la Monte, S. M., & Tong, M. (2009). Mechanisms of nitrosamine-mediated neurodegeneration: Potential relevance to sporadic Alzheimer’s disease. Journal of Alzheimer’s Disease, 17, 817–825.

    PubMed  Google Scholar 

  • de la Monte, S.M., Tong, M., Lawton, M., & Longato, L. (2009). Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment. Molecular Neurodegeneration, 4, 54. http://www.ncbi.nlm.nih.gov/pubmed/20034403 doi: 10.1186/1750-1326-4-54.

  • de la Monte, S. M., Tong, M., Lester-Coll, N., Plater, M., Jr., & Wands, J. R. (2006). Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: Relevance to Alzheimer’s disease. Journal of Alzheimer’s Disease, 10, 89–109.

    PubMed  Google Scholar 

  • de Quervain, D. J., Poirier, R., Wollmer, M. A., Grimaldi, L. M., Tsolaki, M., Streffer, J. R., Hock, C., Nitsch, R. M., Mohajeri, M. H., & Papassotiropoulos, A. (2004). Glucocorticoid-related genetic susceptibility for Alzheimer’s disease. Human Molecular Genetics, 13, 47–52.

    PubMed  Google Scholar 

  • Deng, Y., Li, B., Liu, Y., Iqbal, K., Grundke-Iqbal, I., & Gong, C. X. (2009). Dysregulation of insulin signaling, glucose transporters, O-GlcNAcylation, and phosphorylation of tau and neurofilaments in the brain: Implication for Alzheimer’s disease. The American Journal of Pathology, 175, 2089–2098.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dhull, D. K., Bhateja, D., Dhull, R. K., Padi, S. S. (2012). Differential role of cyclooxygenase isozymes on neuronal density in hippocampus CA1 region of intracerebroventricular streptozotocin treated rat brain. Journal of Chemical Neuroanatomy , 43, 58–51.

    Google Scholar 

  • Diwu, Y. C., Tian, J. Z., & Shi, J. (2011). Effects of Chinese herbal medicine Yinsiwei compound on spatial learning and memory ability and the ultrastructure of hippocampal neurons in a rat model of sporadic Alzheimer disease. Zhong Xi Yi Jie He Xue Bao, 9, 209–215.

    PubMed  Google Scholar 

  • Dudas, B., Hanin, I., Rose, M., & Wülfert, E. (2004). Protection against inflammatory neurodegeneration and glial cell death by 7beta-hydroxy epiandrosterone, a novel neurosteroid. Neurobiology of Disease, 15, 262–268.

    CAS  PubMed  Google Scholar 

  • Duelli, R., Schrock, H., Kuschinsky, W., & Hoyer, S. (1994). Intracerebroventricular injection of streptozotocin induces discrete local changes in cerebral glucose utilization in rats. International Journal of Developmental Neuroscience, 12, 737–743.

    CAS  PubMed  Google Scholar 

  • Evans, D. A., Funkenstein, H. H., Albert, M. S., Scherr, P. A., Cook, N. R., Chown, M. J., Hebert, L. E., Hennekens, C. H., & Taylor, J. O. (1989). Prevalence of Alzheimer’s disease in a community population of older persons. Higher than previously reported. JAMA : The Journal of the American Medical Association, 262, 2551–2556.

    CAS  Google Scholar 

  • Feldmann, R. E., Jr., Maurer, M. H., Hunzinger, C., Lewicka, S., Buergers, H. F., Kalenka, A., Hinkelbein, J., Broemme, J. O., Seidler, G. H., Martin, E., & Plaschke, K. (2008). Reduction in rat phosphatidylethanolamine binding protein-1 (PEBP1) after chronic corticosterone treatment may be paralleled by cognitive impairment: A first study. Stress, 11, 134–147.

    CAS  PubMed  Google Scholar 

  • Fisher, A., Mantione, C. R., Abraham, D. J., & Hanin, I. (1982). Long-term central cholinergic hypofunction induced in mice by ethylcholine aziridinium ion (AF64A) in vivo. The Journal of Pharmacology and Experimental Therapeutics, 222, 140–145.

    CAS  PubMed  Google Scholar 

  • Foster, N. L., Chase, T. N., Mansi, L., Brooks, R., Fedio, P., Patronas, N. J., & Di Chiro, G. (1984). Cortical abnormalities in Alzheimer’s disease. Annals of Neurology, 16, 649–654.

    CAS  PubMed  Google Scholar 

  • Frölich, L., Blum-Degen, D., Bernstein, H. G., Engelsberger, S., Humrich, J., Laufer, S., Muschner, D., Thalheimer, A., Türk, A., Hoyer, S., Zöchling, R., Boissl, K. W., Jellinger, K., & Riederer, P. (1998). Brain insulin and insulin receptors in aging and sporadic Alzheimer’s disease. Journal of Neural Transmission, 105, 423–438.

    PubMed  Google Scholar 

  • Giorgino, F., Chen, J. H., & Smith, R. J. (1992). Changes in tyrosine phosphorylation of insulin receptors and a 170,000 molecular weight nonreceptor protein in vivo in skeletal muscle of streptozotocin-induced diabetic rats: Effects of insulin and glucose. Endocrinology, 130, 1433–1444.

    CAS  PubMed  Google Scholar 

  • Gómez-Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997). Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Annals of Neurology, 41, 17–24.

    PubMed  Google Scholar 

  • Götz, M., Freyberger, A., Hauer, E., Heckers, S., Sofic, E., Jellinger, K., Hebenstreit, G., Beckmann, H., & Riederer, P. (1992). Susceptibility to brains from patients with Alzheimer’s disease to oxygen-stimulated lipid peroxidation and differential scanning calorimetry. Dementia, 3, 213–222.

    Google Scholar 

  • Greenwald, B. S., & Davis, K. L. (1983). Experimental pharmacology of Alzheimer disease. Advances in Neurology, 38, 87–102.

    CAS  PubMed  Google Scholar 

  • Grieb, P., Kryczka, T., Fiedorowicz, M., Frontczak-Baniewicz, M., & Walski, M. (2004). Expansion of the Golgi apparatus in rat cerebral cortex following intracerebroventricular injections of streptozotocin. Acta Neurobiologiae Experimentalis (Wars), 64, 481–489.

    Google Scholar 

  • Grünblatt, E., Salkovic-Petrisic, M., Osmanovic, J., Riederer, P., & Hoyer, S. (2007). Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein. Journal of Neurochemistry, 101, 757–770.

    PubMed  Google Scholar 

  • Grunfeld, C., Baird, K., Van Obberghen, E., & Kahn, C. R. (1981). Glucocorticoid-induced insulin resistance in vitro: Evidence for both receptor and postreceptor defects. Endocrinology, 109(5), 1723–1730.

    CAS  PubMed  Google Scholar 

  • Gsell, W., Conrad, R., Hickethier, M., Sofic, E., Froelich, L., Wichart, I., Jellinger, K., Moll, G., Ransmayr, G., & Beckmann, H. (1995). Decreased catalase activity but unchanged superoxide dismutase activity in brains of patients with dementia of Alzheimer type. Journal of Neurochemistry, 64, 1216–1223.

    CAS  PubMed  Google Scholar 

  • Hardy, J., & Selkoe, D. J. (2002). The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science, 297, 353–356.

    CAS  PubMed  Google Scholar 

  • Hellweg, R., Nitsch, R., Hock, C., Jaksch, M., & Hoyer, S. (1992). Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism. Journal of Neuroscience Research, 31, 479–486.

    CAS  PubMed  Google Scholar 

  • Heo, J. H., Lee, S. R., Lee, S. T., Lee, K. M., Oh, J. H., Jang, D. P., Chang, K. T., & Cho, Z. H. (2011). Spatial distribution of glucose hypometabolism induced by intracerebroventricular streptozotocin in monkeys. Journal of Alzheimer’s Disease, 25, 517–523.

    PubMed  Google Scholar 

  • Holmes, C., Boche, D., Wilkinson, D., Yadegarfar, G., Hopkins, V., Bayer, A., Jones, R. W., Bullock, R., Love, S., Neal, J. W., Zotova, E., & Nicoll, J. A. (2008). Long-term effects of Abeta42 immunisation in Alzheimer’s disease: Follow-up of a randomised, placebo-controlled phase I trial. The Lancet, 372, 216–223.

    CAS  Google Scholar 

  • Hörtnagl, H., Potter, P. E., Singer, E. A., Kindel, G., & Hanin, I. (1989). Clonidine prevents transient loss of noradrenaline in response to cholinergic hypofunction induced by ethylcholine aziridinium (AF64A). Journal of Neurochemistry, 52, 853–858.

    PubMed  Google Scholar 

  • Hoyer, S. (1993). Editor’s Note for debate. Sporadic dementia of Alzheimer type: Role of amyloid in etiology is challenged. Journal of Neural Transmission, 6, 159–165 [P-D Sect].

    CAS  PubMed  Google Scholar 

  • Hoyer, S. (2004a). Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. European Journal of Pharmacology, 490, 115–125.

    CAS  PubMed  Google Scholar 

  • Hoyer, S. (2004b). Causes and consequences of disturbances of cerebral glucose metabolism in sporadic Alzheimer disease: Therapeutic implications. Advances in Experimental Medicine and Biology, 541, 135–152. Review.

    CAS  PubMed  Google Scholar 

  • Hoyer, S., & Lannert, H. (2008). Long-term effects of corticosterone on behavior, oxidative and energy metabolism of parietotemporal cerebral cortex and hippocampus of rats: Comparison to intracerebroventricular streptozotocin. Journal of Neural Transmission, 115, 1241–1249.

    CAS  PubMed  Google Scholar 

  • Hoyer, S., Nitsch, R., & Oesterreich, K. (1991). Predominant abnormality in cerebral glucose utilization in late-onset dementia of the Alzheimer type: A cross-sectional comparison against advanced late-onset and incipient early-onset cases. Journal of Neural Transmission. Parkinson’s Disease and Dementia Section, 3, 1–14.

    CAS  PubMed  Google Scholar 

  • Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996). Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science, 274, 99–102.

    CAS  PubMed  Google Scholar 

  • Ishiguro, K., Shiratsuchi, A., Sato, S., Omori, A., Arioka, M., Kobayashi, S., & Uchida, T. (1993). Glycogen synthase kinase 3-beta is identical to tau protein kinase I generating several epitopes of paired helical filaments. FEBS Letters, 325, 167–172.

    CAS  PubMed  Google Scholar 

  • Ishrat, T., Khan, M. B., Hoda, M. N., Yousuf, S., Ahmad, M., Ansari, M. A., Ahmad, A. S., & Islam, F. (2006). Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behavioural Brain Research, 171, 9–16.

    CAS  PubMed  Google Scholar 

  • Johnston, A. M., Pirola, L., & Van Obberghen, E. (2003). Molecular mechanisms of insulin receptor substrate protein-mediated modulation of insulin signalling. FEBS Letters, 546, 32–36.

    CAS  PubMed  Google Scholar 

  • Joseph, J., Shukitt-Hale, B., Denisova, N. A., Martin, A., Perry, G., & Smith, M. A. (2001). Copernicus revisited: Amyloid beta in Alzheimer’s disease. Neurobiology of Aging, 22(1), 131–146.

    CAS  PubMed  Google Scholar 

  • Kadowaki, T., Kasuga, M., Akanuma, Y., Ezaki, O., & Takaku, F. (1984). Decreased autophosphorylation of the insulin receptor-kinase in streptozotocin-diabetic rats. The Journal of Biological Chemistry, 259, 14208–14216.

    CAS  PubMed  Google Scholar 

  • Kozlowski, M. R., & Arbogast, R. E. (1986). Specific toxic effects of ethylcholine nitrogen mustard on cholinergic neurons of the nucleus basalis of Meynert. Brain Research, 372, 45–54.

    CAS  PubMed  Google Scholar 

  • Kulstad, J. J., McMillan, P. J., Leverenz, J. B., Cook, D. G., Green, P. S., Peskind, E. R., Wilkinson, C. W., Farris, W., Mehta, P. D., & Craft, S. (2005). Effects of chronic glucocorticoid administration on insulin-degrading enzyme and amyloid-beta peptide in the aged macaque. Journal of Neuropathology and Experimental Neurology, 64, 139–146.

    CAS  PubMed  Google Scholar 

  • Kumar, R., Jaggi, A. S., & Singh, N. (2010). Effects of erythropoietin on memory deficits and brain oxidative stress in the mouse models of dementia. The Korean Journal of Physiology and Pharmacology, 14, 345–352.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Landrigan, P. J., Sonawane, B., Butler, R. N., Trasande, L., Callan, R., & Droller, D. (2005). Early environmental origins of neurodegenerative disease in later life. Environmental Health Perspectives, 113, 1230–1233.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lannert, H., & Hoyer, S. (1998). Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats. Behavioral Neuroscience, 112, 1199–1208.

    CAS  PubMed  Google Scholar 

  • Leloup, C., Arluison, M., Lepetit, N., Cartier, N., Marfaing-Jallat, P., Ferre, P., & Penicaud, L. (1994). Glucose transporter 2 (GLUT2): Expression in specific brain nuclei. Brain Research, 638, 221–226.

    CAS  PubMed  Google Scholar 

  • Lester-Coll, N., Rivera, E. J., Soscia, S. J., Doiron, K., Wands, J. R., & de la Monte, S. M. (2006). Intracerebral streptozotocin model of type 3 diabetes: Relevance to sporadic Alzheimer’s disease. Journal of Alzheimer’s Disease, 9, 13–33.

    CAS  PubMed  Google Scholar 

  • Lev-Lehman, E., el-Tamer, A., Yaron, A., Grifman, M., Ginzberg, D., Hanin, I., & Soreq, H. (1994). Cholinotoxic effects on acetylcholinesterase gene expression are associated with brain-region specific alterations in G, C-rich transcripts. Brain Research, 661, 75–82.

    CAS  PubMed  Google Scholar 

  • Lim, D. K., Oh, Y. H., & Kim, H. S. (2001). Impairments of learning and memory following intracerebroventricular administration of AF64A in rats. Archives of Pharmacal Research, 24, 234–239.

    CAS  PubMed  Google Scholar 

  • Mahley, R. W., & Rall, S. C., Jr. (2000). Apolipoprotein E: Far more than a lipid transport protein. Annual Review of Genomics and Human Genetics, 1, 507–537.

    CAS  PubMed  Google Scholar 

  • Mann, D. M., Yates, P. O., & Marcyniuk, B. (1985). Some morphometric observations on the cerebral cortex and hippocampus in presenile Alzheimer’s disease, senile dementia of Alzheimer type and Down’s syndrome in middle age. Journal of the Neurological Sciences, 69, 139–159.

    CAS  PubMed  Google Scholar 

  • Maurer, K., & Hoyer, S. (2006). Alois Alzheimer revisited: Differences in origin of the disease carrying his name. Journal of Neural Transmission, 113, 1645–1658.

    CAS  PubMed  Google Scholar 

  • Mayer, G., Nitsch, R., & Hoyer, S. (1990). Effects of changes in peripheral and cerebral glucose metabolism on locomotor activity, learning and memory in adult male rats. Brain Research, 532, 95–100.

    CAS  PubMed  Google Scholar 

  • Mielke, R., Herholz, K., Grond, M., Kessler, J., & Heiss, W. D. (1994). Clinical deterioration in probable Alzheimer’s disease correlates with progressive metabolic impairment of association areas. Dementia, 5, 36–41.

    CAS  PubMed  Google Scholar 

  • Minoshima, S., Giordani, B., Berent, S., Frey, K. A., Foster, N. L., & Kuhl, D. E. (1997). Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Annals of Neurology, 42, 85–94.

    CAS  PubMed  Google Scholar 

  • Moloney, A. M., Griffin, R. J., Timmons, S., O’Connor, R., Ravid, R., & O’Neill, C. (2010). Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer’s disease indicate possible resistance to IGF-1 and insulin signalling. Neurobiology of Aging, 31, 224–243.

    CAS  PubMed  Google Scholar 

  • Mosconi, L. (2005). Brain glucose metabolism in the early and specific diagnosis of Alzheimer’s disease. FDG-PET studies in MCI and AD. European Journal of Nuclear Medicine and Molecular Imaging, 32, 486–510. Review.

    CAS  PubMed  Google Scholar 

  • Mukhina, T. V., Lermontova, N. N., Van’kin, G. I., Oettel, M., P’chev, V. K., & Bachurin, S. O. (2004). The effects of estrogens on learning in rats with chronic brain cholinergic deficiency in a Morris water test. Identification of the “passive swimming” component. Neuroscience and Behavioral Physiology, 34, 213–219.

    CAS  PubMed  Google Scholar 

  • Nakahara, N., Iga, Y., Mizobe, F., & Kawanishi, G. (1988). Effects of intracerebroventricular injection of AF64A on learning behaviors in rats. Japanese Journal of Pharmacology, 48, 121–130.

    CAS  PubMed  Google Scholar 

  • Ngarmukos, C., Baur, E. L., & Kumagai, A. K. (2001). Co-localization of GLUT1 and GLUT4 in the blood–brain barrier of the rat ventromedial hypothalamus. Brain Research, 900, 1–8.

    CAS  PubMed  Google Scholar 

  • Nitsch, R., & Hoyer, S. (1991). Local action of the diabetogenic drug, streptozotocin, on glucose and energy metabolism in rat brain cortex. Neuroscience Letters, 128, 199–202.

    CAS  PubMed  Google Scholar 

  • Osmanovic, J., Plaschke, K., Salkovic-Petrisic, M., Grünblatt, E., Riederer, P., & Hoyer, S. (2010). Chronic exogenous corticosterone administration generates an insulin-resistant brain state in rats. Stress, 13, 123–131.

    CAS  PubMed  Google Scholar 

  • Ott, A., Breteler, M. M., van Harskamp, F., Claus, J. J., van der Cammen, T. J., Grobbee, D. E., & Hofman, A. (1995). Prevalence of Alzheimer’s disease and vascular dementia: Association with education. The Rotterdam study. BMJ, 310, 970–973.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Park, C. R. (2001). Cognitive effects of insulin in the central nervous system. Neuroscience and Biobehavioral Reviews, 25, 311–323.

    CAS  PubMed  Google Scholar 

  • Park, S. H., & Lim, D. K. (2010). Increases in serotonergic neuronal activity following intracerebroventricular administration of AF64A in rats. Archives of Pharmacal Research, 33, 301–308.

    CAS  PubMed  Google Scholar 

  • Pascualy, M., Petrie, E. C., Brodkin, K., Peskind, E. R., Wilkinson, C. W., & Raskind, M. A. (2000). Hypothalamic pituitary adrenocortical and sympathetic nervous system responses to the cold pressor test in Alzheimer’s disease. Biological Psychiatry, 48, 247–254.

    CAS  PubMed  Google Scholar 

  • Pathan, A. R., Viswanad, B., Sonkusare, S. K., & Ramarao, P. (2006). Chronic administration of pioglitazone attenuates intracerebroventricular streptozotocin induced-memory impairment in rats. Life Sciences, 79, 2209–22016.

    CAS  PubMed  Google Scholar 

  • Phiel, C. J., Wilson, C. A., Lee, V. M. Y., & Klein, P. S. (2003). GSK-3α regulates production of Alzheimer’s disease amyloid-β peptides. Nature, 423, 435–439.

    CAS  PubMed  Google Scholar 

  • Pinton, S., da Rocha, J. T., Gai, B. M., & Nogueira, C. W. (2011). Sporadic dementia of Alzheimer’s type induced by streptozotocin promotes anxiogenic behavior in mice. Behavioural Brain Research, 223, 1–6.

    PubMed  Google Scholar 

  • Plaschke, K., & Hoyer, S. (1993). Action of the diabetogenic drug streptozotocin on glycolytic and glycogenolytic metabolism in adult rat brain cortex and hippocampus. International Journal of Developmental Neuroscience, 11, 477–483.

    CAS  PubMed  Google Scholar 

  • Plaschke, K., Müller, D., & Hoyer, S. (1996). Effect of adrenalectomy and corticosterone substitution on glucose and glycogen metabolism in rat brain. Journal of Neural Transmission, 103, 89–100.

    CAS  PubMed  Google Scholar 

  • Plaschke, K., Müller, D., & Hoyer, S. (2010a). Insulin-resistant brain state (IRBS) changes membrane composition of fatty acids in temporal and entorhinal brain cortices of rats: Relevance to sporadic Alzheimer’s disease? Journal of Neural Transmission, 117, 1419–1422.

    CAS  PubMed  Google Scholar 

  • Plaschke, K., Kopitz, J., Siegelin, M., Schliebs, R., Salkovic-Petrisic, M., Riederer, P., & Hoyer, S. (2010b). Insulin-resistant brain state after intracerebroventricular streptozotocin injection exacerbates Alzheimer-like changes in Tg2576 AbetaPP-overexpressing mice. Journal of Alzheimer’s Disease, 19, 691–704.

    CAS  PubMed  Google Scholar 

  • Ponce-Lopez, T., Liy-Salmeron, G., Hong, E., & Meneses, A. (2011). Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model. Brain Research, 1426, 73–85.

    CAS  PubMed  Google Scholar 

  • Prickaerts, J., Fahrig, T., & Blokland, A. (1999). Cognitive performance and biochemical markers in septum, hippocampus and striatum of rats after an i.c.v. Injection of streptozotocin: A correlation analysis. Behavioural Brain Research, 102, 73–88.

    CAS  PubMed  Google Scholar 

  • Prickaerts, J., De Vente, J., Honig, W., Steinbusch, H., Ittersum, M. M. V., Blokland, A., & Steinbusch, H. W. (2000). Nitric oxide synthase does not mediate neurotoxicity after an i.c.v. Injection of streptozotocin in the rat. Journal of Neural Transmission, 107, 745–766.

    CAS  PubMed  Google Scholar 

  • Qiu, Q. W., & Folstein, M. F. (2006). Insulin, insulin-degrading enzyme and amyloid-β peptide in Alzheimer’s disease: Review and hypothesis. Neurobiology of Aging, 27, 190–198.

    CAS  PubMed  Google Scholar 

  • Qu, Z. Q., Zhou, Y., Zeng, Y. S., Lin, Y. K., Li, Y., Zhong, Z. Q., & Chan, W. Y. (2012). Protective effects of a rhodiola crenulata extract and salidroside on hippocampal neurogenesis against streptozotocin-induced neural injury in the rat. PloS One, 7, e29641.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rivera, E. J., Goldin, A., Fulmer, N., Tavares, R., Wands, J. R., & de la Monte, S. M. (2005). Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: Link to brain reductions in acetylcholine. Journal of Alzheimer’s Disease, 8, 247–268.

    CAS  PubMed  Google Scholar 

  • Salkovic, M., Sabolic, I., & Lackovic, Z. (1995). Striatal dopaminergic D1 and D2 receptors after intracerebroventricular application of alloxan and streptozotocin in rat. Journal of Neural Transmission. General Section, 100, 137–145.

    CAS  PubMed  Google Scholar 

  • Salkovic-Petrisic, M., & Hoyer, S. (2007). Central insulin resistance as a trigger for sporadic Alzheimer-like pathology: An experimental approach. Journal of Neural Transmission. Supplementum, 72, 217–233.

    CAS  PubMed  Google Scholar 

  • Salkovic-Petrisic, M., Tribl, F., Schmidt, M., Hoyer, S., & Riederer, P. (2006). Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathway. Journal of Neurochemistry, 96, 1005–1015.

    CAS  PubMed  Google Scholar 

  • Salkovic-Petrisic, M., Osmanovic, J., Grünblatt, E., Riederer, P., & Hoyer, S. (2009). Modeling sporadic Alzheimer’s disease: The insulin resistant brain state generates multiple long-term morphobiological abnormalities including hyperphosphorylated tau protein and amyloid-beta. Journal of Alzheimer’s Disease, 18, 729–750.

    CAS  PubMed  Google Scholar 

  • Salkovic-Petrisic, M., Osmanovic-Barilar, J., Brückner, M. K., Hoyer, S., Arendt, T., & Riederer, P. (2011). Cerebral amyloid angiopathy in streptozotocin rat model of sporadic Alzheimer’s disease: A long-term follow up study. Journal of Neural Transmission, 118, 765–772.

    CAS  PubMed  Google Scholar 

  • Sandbrink, R., Hartmann, T., Masters, C. L., & Beyreuther, K. (1996). Genes contributing to Alzheimer’s disease. Molecular Psychiatry, 1, 27–40.

    CAS  PubMed  Google Scholar 

  • Saxena, G., Patro, I. K., & Nath, C. (2011). ICV STZ induced impairment in memory and neuronal mitochondrial function: A protective role of nicotinic receptor. Behavioural Brain Research, 224, 50–57.

    CAS  PubMed  Google Scholar 

  • Selkoe, D. J. (2003). Aging, amyloid, and Alzheimer’s disease: A perspective in honor of Carl Cotman. Neurochemical Research, 28, 1705–1713.

    CAS  PubMed  Google Scholar 

  • Sharma, M., & Gupta, Y. K. (2001). Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment. Life Sciences, 68, 1021–1029.

    CAS  PubMed  Google Scholar 

  • Sharma, M., & Gupta, Y. K. (2002). Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats. Life Sciences, 71, 2489–2498.

    CAS  PubMed  Google Scholar 

  • Shoham, S., Bejar, C., Kovalev, E., & Weinstock, M. (2003). Intracerebroventricular injection of streptozotocin causes neurotoxicity to myelin that contributes to spatial memory deficits in rats. Experimental Neurology, 184, 1043–1052.

    CAS  PubMed  Google Scholar 

  • Shoham, S., Bejar, C., Kovalev, E., Schorer-Apelbaum, D., & Weinstock, M. (2007). Ladostigil prevents gliosis, oxidative-nitrative stress and memory deficits induced by intracerebroventricular injection of streptozotocin in rats. Neuropharmacology, 52, 836–843.

    CAS  PubMed  Google Scholar 

  • Snowdon, D. A. (1997). Aging and Alzheimer’s disease: Lessons from the Nun study. The Gerontologist, 37, 150–156.

    CAS  PubMed  Google Scholar 

  • Sonkusare, S., Srinivasan, K., Kaul, C., & Ramarao, P. (2005). Effect of donepezil and lercanidipine on memory impairment induced by intracerebroventricular streptozotocin in rats. Life Sciences, 77, 1–14.

    CAS  PubMed  Google Scholar 

  • Steen, E., Terry, B. M., Rivera, E. J., Cannon, J. L., Neely, T. R., Tavares, R., Xu, X. J., Wands, J. R., & de la Monte, S. M. (2005). Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease–is this type 3 diabetes? Journal of Alzheimer’s Disease, 7, 63–80.

    CAS  PubMed  Google Scholar 

  • Szkudelski, T. (2001). The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological Research, 50, 336–346.

    Google Scholar 

  • Tanzi, R. E., & Bertram, L. (2001). New frontiers in Alzheimer’s disease genetics. Neuron, 32, 181–184.

    CAS  PubMed  Google Scholar 

  • Terwel, D., Prickaerts, J., Meng, F., & Jolles, J. (1995). Brain enzyme activities after intracerebroventricular injection of streptozotocin in rats receiving acetyl-L-carnitine. European Journal of Pharmacology, 287, 65–71.

    CAS  PubMed  Google Scholar 

  • Tong, M., Neusner, A., Longato, L., Lawton, M., Wands, J. R., & de la Monte, S. M. (2009). Nitrosamine exposure causes insulin resistance diseases: Relevance to type 2 diabetes mellitus, non-alcoholic steatohepatitis, and Alzheimer’s disease. Journal of Alzheimer’s Disease, 17, 827–844.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tota, S., Kamat, P. K., Saxena, G., Hanif, K., Najmi, A. K., & Nath, C. (2011). Central angiotensin converting enzyme facilitates memory impairment in intracerebroventricular streptozotocin treated rats. Behavioural Brain Research, 226, 317–330.

    PubMed  Google Scholar 

  • Vallée, M., MacCari, S., Dellu, F., Simon, H., Le Moal, M., & Mayo, W. (1999). Long-term effects of prenatal stress and postnatal handling on age-related glucocorticoid secretion and cognitive performance: A longitudinal study in the rat. The European Journal of Neuroscience, 11, 2906–2916.

    PubMed  Google Scholar 

  • Wada, A., Yokoo, H., Yanagita, T., & Kobayashi, H. (2005). New twist on neuronal insulin receptor signaling in health, disease and therapeutics. Journal of Pharmacological Sciences, 99, 128–143.

    CAS  PubMed  Google Scholar 

  • Watson, G. S., & Craft, S. (2006). Insulin resistance, inflammation, and cognition in Alzheimer’s disease: Lessons for multiple sclerosis. Journal of the Neurological Sciences, 245, 21–33.

    CAS  PubMed  Google Scholar 

  • Weinstock, M., & Shoham, S. (2004). Rat models of dementia based on reductions in regional glucose metabolism, cerebral blood flow and cytochrome oxidase activity. Journal of Neural Transmission, 111, 347–366.

    CAS  PubMed  Google Scholar 

  • Wüppen, K., Oesterle, D., Lewicka, S., Kopitz, J., & Plaschke, K. (2010). A subchronic application period of glucocorticoids leads to rat cognitive dysfunction whereas physostigmine induces a mild neuroprotection. Journal of Neural Transmission, 117, 1055–1065.

    PubMed  Google Scholar 

  • Zhao, W., Chen, H., Xu, H., Moore, E., Meiri, N., Quon, M. J., & Alkon, D. L. (1999). Brain insulin receptors and spatial memory. The Journal of Biological Chemistry, 274, 34893–34902.

    CAS  PubMed  Google Scholar 

  • Zhao, W. Q., Chen, H., Quon, M. H., & Alkon, D. L. (2004). Insulin and the insulin receptor in experimental models of learning and memory. European Journal of Pharmacology, 490, 71–81.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia

    M. Salkovic-Petrisic

  2. Department of Pathology, University of Heidelberg, Heidelberg, Germany

    S. Hoyer

  3. University of Würzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, and National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, Laboratory for Clinical Neurochemistry, Würzburg, Germany

    Peter Riederer

Authors
  1. M. Salkovic-Petrisic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Hoyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Riederer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Riederer .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this entry

Cite this entry

Salkovic-Petrisic, M., Hoyer, S., Riederer, P. (2014). Experimental Approach to Alzheimer Disease. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_98

Download citation

Publish with us

Policies and ethics

Search

Navigation