Animal model for sporadic dementia of Alzheimer’s type (SDAT) using streptozotocin and lipopolysaccharide combinations in rats

https://doi.org/10.19106/JMedSci005203202003

Rahadian Yudo Hartantyo(1*), Mohammad Rizky Mochtar Hidayat(2), Abdul Basith Azzam(3), mulyati mulyati(4)

(1) Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada
(2) Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada
(3) Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada
(4) Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada
(*) Corresponding Author

Abstract


Sporadic dementia of Alzheimer’s type (SDAT) pathogenesis has not been revealed completely due to the difficulty in creating an appropriate animal model. The purpose of this study was to investigate the effect of single-dose intraperitoneal (IP) induction of streptozotocin (STZ) and lipopolysaccharide (LPS) on the β-amyloid levels and the brain function of experimental rats. Eighteen rats were divided into three groups i.e. control, TRE1 (STZ 60 mg.kg-1 BW + LPS 3 mg.kg-1 BW), and TRE2 (STZ 30 mg.kg-1 BW + LPS 1.5 mg.kg-1 BW). The substances were administered in a single dose. Behavioral tests were started at day-30 after injection, we performed Morris water maze (MWM) and novel object recognition (NOR) tests. Afterward, we measured whole brain and serum β-amyloid levels, as one of the biomarkers of Alzheimer’s Disease (AD), using the ELISA method. In MWM tests, the escape latency and time spent in the target quadrant of treatment groups were significantly higher than those in control at the day-5 MWM test and probe trial. The rats in treatment groups have negative discrimination indexes in NOR tasks, indicating that the rats could not remember the familiar object. Intraperitoneal STZ and LPS significantly increase soluble brain β-amyloid levels of treatment groups than those in the control group. In conclusion, the treatment of STZ (60 mg.kg-1 BW) and LPS (3 mg.kg-1 BW) indicated spatial and recognition memory impairment, along with an increase of brain soluble β-amyloid level in rats.


Keywords


β-amyloid; lipopolysaccharide; memory; sporadic dementia; streptozotocin;

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References

  1. Chertkow H, Feldman HH, Jacova C, Massoud F. Definitions of dementia and predementia states in Alzheimer’s disease and vascular cognitive impairment: Consensus from the Canadian conference on diagnosis of dementia. In: Alzheimer’s Research and Therapy. Alzheimers Res Ther 2013; 5(Suppl 1):S2. https://doi.org/10.1186/alzrt198
  2. Duong S, Patel T, Chang F. Dementia: what pharmacists need to know. Can Pharm J (Ott) 2017; 150(2):118-29. https://doi.org/10.1177/1715163517690745
  3. 3. Alzheimer’s Association. 2019 Alzheimer’s disease facts and figures. Alzheimers Dement 2109; 15(3):321-87.
  4. Mc Khann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3):263–9. https://doi.org/10.1016/j/jalz.2011.03.005
  5. Matthews BR. Memory dysfunction. Continuum (Minneap Minn) 2015; 21(3 Behavioral Neurology and Neuropsychiatry): 613-26. https://doi.org/10.1212/01/CON.0000466656.59413.29
  6. Rogers TT, Ivanoiu A, Patterson K, Hodges JR. Semantic memory in Alzheimer’s disease and the frontotemporal dementias: a longitudinal study of 236 patients. Neuropsychology 2006; 20(3):319–35. https://doi.org/10.1037/0894-4105.20.3.319
  7. Pennanen C, Kivipelto M, Tuomainen S, Hartikainen P, Hänninen T, Laakso MP, et al. Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiol Aging 2004; 25(3):303–10. https://doi.org/10.1016/S0197-4580(03)00084-8
  8. El Haj M, Antoine P, Nandrino J-L, Kapogiannis D. Autobiographical memory decline in Alzheimer’s disease. Ageing Res Rev 2016; 27:15-22. https://doi.org/10.1016/j.arr.2016.02.002
  9. Bekris LM, Yu CE, Bird TD, Tsuang DW. Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol 2010; 23(4):213-27. https://doi.org/10.1177/0891988710383571
  10. Lanoiselée HM, Nicolas G, Wallon D, Rovelet-Lecrux A, Lacour M, Rousseau S, et al. APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Med 2017; 14(3):e1002270. http://doi.org/10.1371/journal.pmed.1002270
  11. Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur J Neurol 2018; 25(1):59–70. https://doi.org/10.111/ene.13439
  12. Raulin AC, Kraft L, Al-Hilaly YK, Xue WF, McGeehan JE, Atack JR, et al. The molecular basis for apolipoprotein E4 as the major risk factor for late-onset Alzheimer’s disease. J Mol Biol 2019; 431(12):2248-65. https://doi.org/10.1016/j.jmb.2019.04.019.
  13. Sanabria-Castro A, Alvarado-Echeverría I, Monge-Bonilla C. Molecular pathogenesis of Alzheimer’s disease. Ann Neurosci 2017; 24(1):46-54. https://doi.org/10.1159/000464422
  14. Ferreira ST, Lourenco M V., Oliveira MM, De Felice FG. Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer’s disease. Front Cell Neurosci 2015; 9:191. https://doi.org.10.3389/fncel.2015.00191
  15. Grieb P. Intracerebroventricular streptozotocin injections as a model of Alzheimer’s disease: in search of a relevant mechanism. Mol Neurobiol 2016; 53(3):174152. https://doi.org/10.1007/s12035-015-9132-3
  16. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 2001; 50(6):537-46.
  17. Nahdi AMTA, John A, Raza H. Elucidation of molecular mechanisms of streptozotocin-induced oxidative stress, apoptosis, and mitochondrial dysfunction in Rin-5F pancreatic β-cells. Oxid Med Cell Longev 2017; 2017:7054272 https://doi.org/10.1155/2017/7054272
  18. Friederich M, Hansell P, Palm F. Diabetes, oxidative stress, nitric oxide and mitochondria function. Curr Diabetes 2009; 5(2):120-44. http://doi.org/10.2174/157339909788166800
  19. Kahraman S, Aydin C, Elpek GO, Dirice E, Sanlioglu AD. Diabetes-resistant NOR mice are more severely affected by streptozotocin compared to the diabetes-prone NOD mice: correlations with liver and kidney GLUT2 expressions. J Diabetes Res 2015; 2015:450128 https://doi.org/10.1155/2015/450128
  20. Arluison M, Quignon M, Nguyen P, Thorens B, Leloup C, Penicaud L. Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain - An immunohistochemical study. J Chem Neuroanat 2004; 28(3):117–36. https://doi.org/10.1016/j.jchemneu.2004.05.009
  21. Vorhees CV, Williams MT. Morris water maze: Procedures for assessing spatial and related forms of learning and memory. Nat Protoc 2006; 1(2):848–58. https://doi.org/10.1038/nprot.2006.116
  22. Antunes M, Biala G. The novel object recognition memory: Neurobiology, test procedure, and its modifications Cogn Process 2012; 13:93-110. https://doi.org/10.1007/s10339-011-0430-z
  23. Casali B, Landreth G. Aβ Extraction from murine brain homogenates. Bio Protoc 2016; 6(8):e1787 https://doi.org/10.21769/BioProtoc.1787
  24. Kopelman MD. Disorders of memory. Brain 2002; 125(pt 10):2152–90. https://doi.org/10.1093/brain/awf229
  25. Moser MB, Rowland DC, Moser EI. Place cells, grid cells, and memory. Cold Spring Harb Perspect Biol 2015; 7(2):a021808. https://doi.org/10.1101/cshperspect.a021808
  26. Eteghad SS, Sabermarouf B, Majdi A, Talebi M, Farhoudi M, Mahmoudi J. Amyloid-beta: a crucial factor in Alzheimer’s disease. Med Princ Pract 2015; 24(1):1–10. https://doi.org/10.1159/000369101
  27. Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science 1992; 256(5054):184–5. https://doi.org/10.1126/science.1566067
  28. Shankar GM, Walsh DM. Alzheimer’s disease: Synaptic dysfunction and Aβ. Mol Neurodegener 2009;4:48. https://doi.org/10.1186/1750-1326-4-48
  29. Moreira PI, Carvalho C, Zhu X, Smith MA, Perry G. Mitochondrial dysfunction is a trigger of Alzheimer’s disease pathophysiology. Biochim Biophys Acta 2010; 1802(1):2-10. https://doi.org/10.1016/j.bbadis.2009.10.006
  30. Korte M, Herrmann U, Zhang X, Draguhn A. The role of APP and APLP for synaptic transmission, plasticity, and network function: Lessons from genetic mouse models. Exp Brain Res 2012; 217(3-4):435-40. http://doi.org/10.1007/s00221-011-2894-6
  31. Wang LM, Wu Q, Kirk RA, Horn KP, Ebada Salem AH, Hoffman JM, et al. Lipopolysaccharide endotoxemia induces amyloid-β and p-tau formation in the rat brain. Am J Nucl Med Mol Imaging 2018; 8(2):86–99.
  32. Jendresen C, Digre A, Cui H, Zhang X, Vlodavsky I, Li JP, et al. Systemic LPS-induced Aβ-solubilization and clearance in AβPP-transgenic mice is diminished by heparanase overexpression. Sci Rep 2019; 9(1):4600. https://doi.org/10.1038/s41598-019-40999-4
  33. Lecanu L, Papadopoulos V. Modeling Alzheimer’s disease with non-transgenic rat models. Alzheimers Res Ther 2013; 5(3):17. https://doi.org/10.1186/alzrt171
  34. Gilles C, Ertlé S, Macher JP. Pharmacological models in Alzheimer’s disease research. Dialogues Clin Neurosci 2000; 2:247-55.
  35. Nilsberth C, Kostyszyn B, Luthman J. Changes in APP, PS1 and other factors related to Alzheimer’s disease pathophysiology after trimethyltin-induced brain lesion in the rat. Neurotox Res 2002; 4(7-8):625–36.



DOI: https://doi.org/10.19106/JMedSci005203202003

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