Modeling of age-dependent disorders: relationship between the nervous and endocrine systems

Cover Page


Cite item

Full Text

Abstract

Age-dependent disorders are a challenging problem of modern society. Among the most significant age-dependent disorders are Alzheimer's disease (AD), diabetes, metabolic syndrome, etc.; these conditions may be associated to each other and have, at least in part, an interconnecting character. An experimental model of AD induced by intracerebroventricular administration of streptozocin (STZ) mimics some key characteristics of sporadic AD, altering insulin metabolism. The aim of this work was to study glucose metabolism in rats at different periods after intracerebroventricular injection of STZ. To obtain an AD model, STZ in a 0.9% NaCl solution at a dose of 3 mg/kg in 10 μl was administered bilaterally in the brain lateral ventricles on stereotaxic operations. Two and seven weeks after the administration, the weight of the animals was determined, and the glucose levels in tail vein whole blood after intraperitoneal glucose administration at a dose of 1.5 g/kg was measured. A standard glucose tolerance test was performed, and hyperglycemic and postglycemic ratios were calculated. As a result, an impairment of glucose metabolism in rats 7 weeks after intracerebroventricular application of STZ was detected for the first time. Close connection of Alzheimertype neurodegenerative changes and glucose metabolism revealed on this model allows using it for deeper assessment of relationships between the nervous and endocrine systems, including translational studies of novel therapeutic strategies.

About the authors

Alla V. Stavrovskaya

Research Center of Neurology

Author for correspondence.
Email: alla_stav@mail.ru
Россия, Moscow

Dmitriy N. Voronkov

Research Center of Neurology

Email: alla_stav@mail.ru
Россия, Moscow

Ekaterina A. Shestakova

National Medical Research Center of Endocrinology

Email: alla_stav@mail.ru
Россия, Moscow

Artyem S. Ol’shansky

Research Center of Neurology

Email: alla_stav@mail.ru
Россия, Moscow

Nina G. Yamshchikova

Research Center of Neurology

Email: alla_stav@mail.ru
Россия, Moscow

Anastasia S. Gushchina

Research Center of Neurology

Email: alla_stav@mail.ru
Россия, Moscow

Sergey N. Illarioshkin

Research Center of Neurology

Email: alla_stav@mail.ru
Россия, Moscow

References

  1. Chen Y., Liang Z., Blanchard J. et al. A non-transgenic mouse model (icv-STZ mouse) of Alzheimer’s disease: similarities to and differences from the transgenic model (3xTg-AD mouse). Mol Neurobiol 2013; 47(2): 711-725. doi: 10.1007/s12035-012-8375-5. PMID: 23150171.
  2. Hoyer S., Lee S.K., Löffler T., Schliebs R. Inhibition of the neuronal insulin receptor. An in vivo model for sporadic Alzheimer disease? Ann N YAcad Sci 2000; 920: 256–258. doi: 10.1111/j.1749-6632.2000.tb06932.x. PMID: 11193160.
  3. Hau J. Animal models of human diseases. In: Conn PM (ed) An overview. (in:) Sourcebook of Models for Biomedical Research, Humana Press, Totowa, 2008; 1: 15–20. DOI: org/10.1007/978-1-59745-285-4_1.
  4. Iqbal K., Bolognin S., Wang X. et al. Animal models of the sporadic form of Alzheimer’s disease: Focus on the disease and not just the lesions. J Alzheimers Dis 2013; 37: 469–474. doi: 10.3233/JAD-130827. PMID: 23948903.
  5. Shineman D.W., Basi G.S., Bizon J.L. et al Accelerating drug discovery for Alzheimer’s disease: best practices for preclinical animal studies. Alzheimers Res Ther 2011; 3: 28. doi: 10.1186/alzrt90. PMID: 21943025.
  6. Ganda O.P., Rossini A.A., Like A.A. Studies on streptozotocin diabetes. Dia-betes 1976; 25: 595–603. doi: 10.2337/diab.25.7.595. PMID: 132382.
  7. Degenhardt T.P., Alderson N.L., Arrington D.D. et al. Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocindiabetic rat. Kidney Int2002; 61: 939–950 doi: 10.1046/j.1523-1755.2002.00207.x. PMID: 11849448.
  8. Srinivasan K., Viswanad B., Asrat L. et al. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and phar-macological screening. Pharmacol Res 2005; 52: 313–320. doi: 10.1016/j.phrs.2005.05.004. PMID: 15979893.
  9. Reaven G.M. Banting lecture 1988. Role of insulin resistance in human dis-ease. Diabetes 1988; 37(12): 1595–1607. doi: 10.1016/0899-9007(97)90878-9. PMID: 3056758.
  10. Grundy S.M. Metabolic Syndrome update. Trends Cardiovasc Med 2016; 26: 364–373 doi: 10.1016/j.tcm.2015.10.004. PMID: 26654259.
  11. Tanashyan M.M., Lagoda O.V., Antonova K.V. [Chronic cerebrovascular diseases in metabolic syndrome: new approaches to the treatment]. Zhurnal nev-rologii i psikhiatrii im. S.S. Korsakova 2012; 112(11): 21-26 (In Russ.)
  12. . Du L.L., Chai D.M., Zhao L.N. et al. AMPK activation ameliorates Alzhei-mer’s disease-like pathology and spatial memory impairment in a streptozotocin induced Alzheimer’s disease model in rats. J Alzheimers Dis 2015; 43(3): 775-784. doi: 10.3233/JAD-140564. PMID: 25114075.
  13. Yang W., Ma J., Liu Z. et al. Effect of naringenin on brain insulin signaling and cognitive functions in ICV-STZ induced dementia model of rats. Neurol Sci2014; 35(5): 741-751. doi: 10.1007/s10072-013-1594-3. PMID: 24337945.
  14. Prakash A., Kalra J.K., Kumar A. Neuroprotective effect of N-acetyl cys-teine against streptozotocin-induced memory dysfunction and oxidative dam-age in rats. J Basic Clin Physiol Pharmacol 2015; 26(1): 13-23. doi: 10.1515/jbcpp-2013-0150. PMID:: 24756058.
  15. Salkovic-Petrisic M., Knezovic A., Hoyer S. et al. What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research. J Neural Transm 2013; 120: 233–252. doi: 10.1007/s00702-012-0877-9. PMID: 22886150.
  16. Correia S.C., Santos R.X., Santos M.S. et al. Mitochondrial abnormalities in a streptozotocin-induced rat model of sporadic Alzheimer’s disease. Curr Alzhei-mer Res 2013; 10: 406–419. PMID: 23061885.
  17. Ishrat T., Hoda M.N., Khan M.B. et al. Amelioration of cognitive deficits and neurodegeneration by curcumin in rat model of sporadic dementia of Alz-heimer’s type (SDAT). Eur Neuropsychopharmacol 2009; 19: 636–647. doi: 10.1016/j.euroneuro.2009.02.002. PMID: 19329286.
  18. Paxinos G., Watson Ch. The rat brain in stereotaxic coordinates. 4th edition. Acafemic Press, 1998.
  19. Goryacheva M.A., Makarova M.N. [Features of the glucose tolerance test in small laboratory rodents (mice and rats)]. Mezhdunarodnyi vestnik veterinarii 2016; 3: 155-159 (In Russ.)
  20. . Nazarenko G.I., Kishkun A.A. Klinicheskaya otsenka rezul’tatov labora-tornykh issledovaniy [Clinical evaluation of laboratory results] Moscow: Med-itsina 2000. 544p. (In Russ.)
  21. Junod A., Lambert A.E., Stauffacher W. et al. Diabetogenic action of strep-tozotocin: relationship of dose to metabolic response. J Clin Invest 1969; 48: 2129–2139. doi: 10.1172/JCI106180. PMID: 4241908.
  22. Lanfray D., Arthaud S., Ouellet J. et al. Gliotransmission and brain glucose sensing: critical role of endozepines. Diabetes 2013; 62: 801–810. doi: 10.2337/db11-0785. PMID: 23160530.
  23. Grünblatt E., Salkovic-Petrisic M., Osmanovic J. et al. Brain insulin sys-tem dysfunction in streptozotocin intracerebroventricularly treated rats gener-ates hyperphosphorylatedtau protein. J Neurochem 2007; 101: 757–770. doi: 10.1111/j.1471-4159.2006.04368.x. PMID: 17448147.
  24. Knezovic А., Loncar A., Homolak J. et al. Rat brain glucose transporter-2, insulin receptor and glial expression are acute targets of intracerebroventricular streptozotocin: risk factors for sporadic Alzheimer’s disease? J Neural Transm2017; 124(6): 695–708. doi: 10.1007/s00702-017-1727-6. PMID: 28470423.
  25. de la Monte S.M. Type 3 diabetes is sporadic Alzheimer s disease: Mini-re-view. Eur Neuropsychopharmacol 2014; 24: 1954–1960. doi: 10.1016/j.euroneu-ro.2014.06.008. PMID: 25088942.
  26. de la Monte S.M., Tong M. Brain metabolic dysfunction at the core of Alzheimer’s disease. Biochem Pharmacol 2014; 88: 548–559. doi: 10.1016/j.bcp.2013.12.012. PMID: 24380887.
  27. Lester-Coll N., Rivera E.J., Soscia S.J. et al. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer’s disease. J Alzheimers Dis 2006; 9: 13–33. doi: 10.3233/JAD-2006-9102. PMID: 16627931.
  28. de la Monte S.M., Tong M., Lester-Coll N. et al. Therapeutic rescue of neu-rodegeneration in experimental type 3 diabetes: relevance to Alzheimer’s disease. J Alzheimers Dis 2006; 10: 89–109. doi: 10.3233/JAD-2006-10113. PMID: 16988486.
  29. . Iliff J.J., Wang M., Liao Y. et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med 2012; 4: 147. doi: 10.1126/scitranslmed.3003748. PMID: 22896675.
  30. Blondel O., Portha B. Early appearance of in vivo insulin resistance in adult streptozotocin-injected rats. Diabete Metab 1989; 15: 382–387. PMID: 2697607.
  31. Ju C., Yue W., Yang Z. et al. Antidiabetic effect and mechanism of chi-tooligosaccharides. Biol Pharm Bull 2010; 33(9): 1511–1516. doi: 10.1248/bpb.33.1511. PMID: 20823566.
  32. Panchal S.K., Poudyal H., Iyer A. et al. High-carbohydrate, high-fat di-et-induced metabolic syndrome and cardiovascular remodeling in rats. J Car-diovasc Pharmacol 2011; 57(5): 611–624. doi: 10.1097/FJC.0b013e3181feb90a. PMID: 21572266.
  33. Fine J.M., Forsberg A.C., Stroebel B.M. et al. Intranasal deferoxamine af-fects memory loss, oxidation, and the insulin pathway in the streptozotocin rat model of Alzheimer’s disease. J Neurol Sci 2017; 380: 164-171. doi: 10.1016/j.jns.2017.07.028. PMID: 28870559.
  34. Ayala J.E., Bracy D.P., McGuinness O.P. et al. Considerations in the design of hyperinsulinemic-euglycemic clamps in the conscious mouse. Diabetes 2006; 55: 390–397. doi: 10.2337/diabetes.55.02.06.db05-0686. PMID: 16443772.
  35. Muniyappa R., Lee S., Chen H. et al. Current approaches for assessing in-sulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 2008; 294: 15–26. doi: 10.1152/ajpen-do.00645.2007. PMID: 17957034.
  36. Butakova S.S., Nozdrachyov A.D. [Effect of calcitonin on the nature of nu-tritional hyperglycemia in rats of different ages and sexes]. Uspekhi gerontologii2010; 23(2): 213-220 (In Russ.)
  37. Knezovic A., Osmanovic-Barilar J., Curlin M. et al. Staging of cognitive defi-cits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer’s disease. J Neural Transm 2015; 122(4): 577-592. doi: 10.1007/s00702-015-1394-4 PMID: 25808906.
  38. Morales R., Duran-Aniotz C., Castilla J. et al. De novo induction of amy-loid-β deposition in vivo. Mol Psychiatry 2012; 17(12): 1347-53. doi: 10.1038/mp.2011.120. PMID: 21968933

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2018 Stavrovskaya A.V., Voronkov D.N., Shestakova E.A., Ol’shansky A.S., Yamshchikova N.G., Gushchina A.S., Illarioshkin S.N.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-83204 от 12.05.2022.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies