Effect of Lipopolysaccharide in Inflammation of the Brain and Induction of Alzheimer's Disease in Male Wistar Rat

Document Type : Original Article (s)

Authors

1 Department of Animal Physiology, School of Biology, Kharazmi University, Tehran, Iran

2 Professor, Department of Animal Physiology, School of Biology, Kharazmi University, Tehran, Iran

3 Assistant Professor, Department of Biology, School of Science, Lorestan University, Khorramabad, Iran

Abstract

Background: Alzheimer's disease is a disease of the nerve cells that is associated with neurodegeneration; including the weakening of nerve cells, as the cells show inflammatory activities. In this research, the effects of lipopolysaccharide (LPS) in inflammation in the rat hippocampus, as well as its effect on cell death were studied.Methods: The effects of intraperitoneal injection of lipopolysaccharide in the development of inflammation in the nerve cells in the hippocampus of Wistar rats with the weight of 230-250 g was assessed via measuring the levels of inflammatory factors [interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α)] using Western blot analysis. The study of cell death was done using Hematoxylin and Eosin staining (H&E) in a time-dependent manner at 12, 24, 48, 72 and 120 hours after the injection.Findings: The amounts of inflammatory proteins, IL-1β and TNF-α, increased time-dependently as compared to the control group. The stained tissue confirmed the cell death. All the results were significant at the level of P < 0.001.Conclusion: Lipopolysaccharide causes inflammation and neuronal cell death in the hippocampus in the brain of male Wistar rats; which is a time-dependent apoptosis in these cells and induces development of Alzheimer's process, then.

Keywords


  1. Mufson EJ, Counts SE, Perez SE, Ginsberg SD. Cholinergic system during the progression of Alzheimer's disease: therapeutic implications. Expert Rev Neurother 2008; 8(11): 1703-18.
  2. Selkoe DJ. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature 1999; 399(Suppl): A23-A31.
  3. Kandel E, Schwartz J, Jessell T. Principles of neural science. 4th ed. New York, NY: McGraw-Hill Medical; 2000.
  4. Dantzer R. Cytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity. Eur J Pharmacol 2004; 500(1-3): 399-411.
  5. Allan SM, Tyrrell PJ, Rothwell NJ. Interleukin-1 and neuronal injury. Nat Rev Immunol 2005; 5(8): 629-40.
  6. McGeer EG, McGeer PL. Inflammatory processes in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27(5): 741-9.
  7. Rivest S. Molecular insights on the cerebral innate immune system. Brain Behav Immun 2003; 17(1): 13-9.
  8. Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, et al. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 1999; 11(4): 443-51.
  9. Hoebe K, Janssen E, Beutler B. The interface between innate and adaptive immunity. Nat Immunol 2004; 5(10): 971-4.
  10. Tanaka S, Ide M, Shibutani T, Ohtaki H, Numazawa S, Shioda S, et al. Lipopolysaccharide-induced microglial activation induces learning and memory deficits without neuronal cell death in rats. J Neurosci Res 2006; 83(4): 557-66.
  11. Breitner JC, Gau BA, Welsh KA, Plassman BL, McDonald WM, Helms MJ, et al. Inverse association of anti-inflammatory treatments and Alzheimer's disease: initial results of a co-twin control study. Neurology 1994; 44(2): 227-32.
  12. Breitner JC, Welsh KA, Helms MJ, Gaskell PC, Gau BA, Roses AD, et al. Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs. Neurobiol Aging 1995; 16(4): 523-30.
  13. Sun WH, Chen GS, Ou XL, Yang Y, Luo C, Zhang Y, et al. Inhibition of COX-2 and activation of peroxisome proliferator-activated receptor gamma synergistically inhibits proliferation and induces apoptosis of human pancreatic carcinoma cells. Cancer Lett 2009; 275(2): 247-55.
  14. Quan N, Sundar SK, Weiss JM. Induction of interleukin-1 in various brain regions after peripheral and central injections of lipopolysaccharide. J Neuroimmunol 1994; 49(1-2): 125-34.
  15. McGeer EG, McGeer PL. The importance of inflammatory mechanisms in Alzheimer disease. Exp Gerontol 1998; 33(5): 371-8.
  16. Dickson DW, Lee SC, Mattiace LA, Yen SH, Brosnan C. Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. Glia 1993; 7(1): 75-83.
  17. Heumann D, Roger T. Initial responses to endotoxins and Gram-negative bacteria. Clin Chim Acta 2002; 323(1-2): 59-72.
  18. Quan N1, He L, Lai W, Shen T, Herkenham M. Induction of IkappaBalpha mRNA expression in the brain by glucocorticoids: a negative feedback mechanism for immune-to-brain signaling. J Neurosci. 2000; 20(17): 6473-7.
  19. Cakala M, Malik AR, Strosznajder JB. Inhibitor of cyclooxygenase-2 protects against amyloid beta peptide-evoked memory impairment in mice. Pharmacol Rep 2007; 59(2): 164-72.
  20. Oryan Sh, Nazari-Serenjeh M, Bagherpoor-Zarchi M, Khodagholi F, Nabiuni M, Shahzamani K. Effect of intraperitoneal injection of lipopolysaccharide (LPS) on apoptosis, memory and Alzheimer's disease processes in the hippocampus of male wistar rats in a time-dependent manner. J Isfahan Med Sch 2014; 32(285): 650-9. [In Persian].
  21. Loscher CE, Donnelly S, Mills KH, Lynch MA. Interleukin-1beta-dependent changes in the hippocampus following parenteral immunization with a whole cell pertussis vaccine. J Neuroimmunol 2000; 111(1-2): 68-76.
  22. Lonergan PE, Martin DS, Horrobin DF, Lynch MA. Neuroprotective actions of eicosapentaenoic acid on lipopolysaccharide-induced dysfunction in rat hippocampus. J Neurochem 2004; 91(1): 20-9.
  23. Zimmermann KC, Bonzon C, Green DR. The machinery of programmed cell death. Pharmacol Ther 2001; 92(1): 57-70.