Skip to main content

Advertisement

SpringerLink
Log in

Effects of immune activation on the retrieval of spatial memory

免疫激活对空间记忆提取的影响

  • Original Article
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Objective

It has been shown that there are extensive interactions between the central nervous system and the immune system. The present study focused on the effects of lipopolysaccharide (LPS) on memory retrieval, to explore the interaction between immune activation and memory.

Methods

C57BL/6J mice (8 weeks old) were first trained in the Morris water maze to reach asymptotic performance. Then mice were tested 24 h after the last training session and LPS was administered (1.25 mg/kg, i.p.) 4 h prior to the testing. The retrieval of spatial memory was tested by probe trial, and the time spent in the target quadrant and the number of platform location crosses were recorded. ELISA was performed to detect interleukin-1β (IL-1β) protein level in the hippocampus of mice tested in the water maze.

Results

Although LPS induced overt sickness behavior and a significant increase in the level of IL-1β in the hippocampus of mice, there was no significant difference in the time spent in the target quadrant or in the number of platform location crosses between LPS-treated and control groups in the probe trial testing.

Conclusion

Immune activation induced by LPS does not impair the retrieval of spatial memory.

摘要

目的

神经系统和免疫系统之间存在广泛的相互作用。 许多研究表明, 细菌脂多糖(lipopolysaccharide, LPS)或白介素1β 引起的免疫激活会造成学习记忆的损伤。 但也有一些研究报道免疫激活对学习记忆几乎没有影响。 因此, 免疫激活与学习记忆损伤之间的关系尚不十分清楚。 本研究旨在检测LPS 对空间记忆提取的影响, 探讨免疫激活与记忆之间的相互作用。

方法

先在水迷宫中训练 琪琪8 周龄C57BL/6J 系小鼠, 随后小鼠腹腔注射LPS 并进行空间觅向能力测试。 记录小鼠在目标象限游泳的时间和穿过原平台位置的次数, 以判断动物记忆提取再现能力。 用酶联免疫法检测小鼠海马中白介素1β 的水平。

结果

LPS 能引起小鼠产生明显的病态行为, 并导致海马中白介素1β的水平显著升高。 注射LPS的小鼠在目标象限游泳的时间以及穿越逃生台位置的次数与对照组小鼠相比没有显著差异。

结论

LPS 引起的免疫激活并不损害空间记忆的提取。

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Maier SF, Watkins LR. Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychol Rev 1998, 105: 83–107.

    Article  PubMed  CAS  Google Scholar 

  2. Dantzer R, Bluthe RM, Kent S, Goodall G. Behavioral effects of cytokines: An insight into mechanisms of sickness behavior. In: E. G. DeSouza (Ed.), Neurobiology of cytokines. San Diego: Academic Press, 1993: 130–151.

    Google Scholar 

  3. Ek M, Kurosawa M, Lundeberg T, Ericsson A. Activation of vagal afferents after intravenous injection of interleukin-1beta: role of endogenous prostaglandins. J Neurosci 1998, 18: 9471–9479.

    PubMed  CAS  Google Scholar 

  4. Konsman JP, Tridon V, Dantzer R. Diffusion and action of intracerebroventricularly injected interleukin-1 in the CNS. Neuroscience 2000, 101: 957–967.

    Article  PubMed  CAS  Google Scholar 

  5. Vitkovic L, Konsman JP, Bockaert J, Dantzer R, Homburger V, Jacque C. Cytokine signals propagate through the brain. Mol Psychiatry 2000, 5: 604–615.

    Article  PubMed  CAS  Google Scholar 

  6. Cunningham ET, De Souza EB. Interleukin 1 receptors in the brain and endocrine tissues. Immunol Today 1993, 14: 171–176.

    Article  PubMed  CAS  Google Scholar 

  7. Weiss JM, Quan N, Sundar SK. Widespread activation and consequences of interleukin-1 in the brain. Ann N Y Acad Sci 1994, 741: 338–357.

    Article  PubMed  CAS  Google Scholar 

  8. Loddick SA, Liu C, Takao T, Hashimoto K, De Souza EB. Interleukin-1 receptors: cloning studies and role in central nervous system disorders. Brain Res Brain Res Rev 1998, 26: 306–319.

    Article  PubMed  CAS  Google Scholar 

  9. Schneider H, Pitossi F, Balschun D, Wagner A, del Rey A, Besedovsky HO. A neuromodulatory role of interleukin-1beta in the hippocampus. Proc Natl Acad Sci U S A 1998, 95: 7778–7783.

    Article  PubMed  CAS  Google Scholar 

  10. Avital A, Goshen I, Kamsler A, Segal M, Iverfeldt K, Richter-Levin G, et al. Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity. Hippocampus 2003, 13: 826–834.

    Article  PubMed  CAS  Google Scholar 

  11. Ban E, Haour F, Lenstra R. Brain interleukin 1 gene expression induced by peripheral lipopolysaccharide administration. Cytokine 1992, 4: 48–54.

    Article  PubMed  CAS  Google Scholar 

  12. Laye S, Parnet P, Goujon E, Dantzer R. Peripheral administration of lipopolysaccharide induces the expression of cytokine transcripts in the brain and pituitary of mice. Brain Res Mol Brain Res 1994, 27: 157–162.

    Article  PubMed  CAS  Google Scholar 

  13. Buttini M, Boddeke H. Peripheral lipopolysaccharide stimulation induces interleukin-1 beta messenger RNA in rat brain microglial cells. Neuroscience 1995, 65: 523–530.

    Article  PubMed  CAS  Google Scholar 

  14. Nguyen KT, Deak T, Owens SM, Kohno T, Fleshner M, Watkins LR, et al. Exposure to acute stress induces brain interleukin-1beta protein in the rat. J Neurosci 1998, 18: 2239–2246.

    PubMed  CAS  Google Scholar 

  15. Arai K, Matsuki N, Ikegaya Y, Nishiyama N. Deterioration of spatial learning performances in lipopolysaccharide-treated mice. Jpn J Pharmacol 2001, 87: 195–201.

    Article  PubMed  CAS  Google Scholar 

  16. Lee JW, Lee YK, Yuk DY, Choi DY, Ban SB, Oh KW, et al. Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J Neuroinflammation 2008, 5: 37.

    Article  PubMed  CAS  Google Scholar 

  17. Shaw KN, Commins S, O’Mara SM. Lipopolysaccharide causes deficits in spatial learning in the watermaze but not in BDNF expression in the rat dentate gyrus. Behav Brain Res 2001, 124: 47–54.

    Article  PubMed  CAS  Google Scholar 

  18. Sparkman NL, Martin LA, Calvert WS, Boehm GW. Effects of intraperitoneal lipopolysaccharide on Morris maze performance in year-old and 2-month-old female C57BL/6J mice. Behav Brain Res 2005, 159: 145–151.

    Article  PubMed  CAS  Google Scholar 

  19. Sparkman NL, Kohman RA, Garcia AK, Boehm GW. Peripheral lipopolysaccharide administration impairs two-way active avoidance conditioning in C57BL/6J mice. Physiol Behav 2005, 85: 278–288.

    Article  PubMed  CAS  Google Scholar 

  20. Pavlov IP. Conditioned reflexes. New York: Dover 1960.

    Google Scholar 

  21. William James. The principles of psychology. New York: Holt 1890.

    Google Scholar 

  22. Terry AV Tr. Spatial Navigation (Water Maze) Tasks. In: Buccafusco JJ (Ed.). Methods of Behavior Analysis in Neuroscience. Boca Raton: CRC Press, 2001: 164–177.

    Google Scholar 

  23. Konsman JP, Kelley K, Dantzer R. Temporal and spatial relationships between lipopolysaccharide-induced expression of Fos, interleukin-1beta and inducible nitric oxide synthase in rat brain. Neuroscience 1999, 89: 535–548.

    Article  PubMed  CAS  Google Scholar 

  24. Van Dam AM, Bauer J, Tilders FJ, Berkenbosch F. Endotoxin-induced appearance of immunoreactive interleukin-1 beta in ramified microglia in rat brain: a light and electron microscopic study. Neuroscience 1995, 65: 815–826.

    Article  PubMed  Google Scholar 

  25. Quan N, Whiteside M, Herkenham M. Time course and localization patterns of interleukin-1beta messenger RNA expression in brain and pituitary after peripheral administration of lipopolysaccharide. Neuroscience 1998, 83: 281–293.

    Article  PubMed  CAS  Google Scholar 

  26. Gabellec MM, Griffais R, Fillion G, Haour F. Expression of interleukin 1 alpha, interleukin 1 beta and interleukin 1 receptor antagonist mRNA in mouse brain: regulation by bacterial lipopolysaccharide (LPS) treatment. Brain Res Mol Brain Res 1995, 31: 122–130.

    Article  PubMed  CAS  Google Scholar 

  27. Irwin S. Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia 1968, 13: 222–257.

    Article  PubMed  CAS  Google Scholar 

  28. Aubert A, Vega C, Dantzer R, Goodall G. Pyrogens specifically disrupt the acquisition of a task involving cognitive processing in the rat. Brain Behav Immun 1995, 9: 129–148.

    Article  PubMed  CAS  Google Scholar 

  29. Pugh CR, Kumagawa K, Fleshner M, Watkins LR, Maier SF, Rudy JW. Selective effects of peripheral lipopolysaccharide administration on contextual and auditory-cue fear conditioning. Brain Behav Immun 1998, 12: 212–229.

    Article  PubMed  CAS  Google Scholar 

  30. Sparkman NL, Kohman RA, Scott VJ, Boehm GW. Bacterial endotoxin-induced behavioral alterations in two variations of the Morris water maze. Physiol Behav 2005, 86: 244–251.

    Article  PubMed  CAS  Google Scholar 

  31. Liaudet L, Murthy KG, Mabley JG, Pacher P, Soriano FG, Salzman AL, et al. Comparison of inflammation, organ damage, and oxidant stress induced by Salmonella enterica serovar Muenchen flagellin and serovar Enteritidis lipopolysaccharide. Infect Immun 2002, 70: 192–198.

    Article  PubMed  CAS  Google Scholar 

  32. Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, et al. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 2007, 55: 453–462.

    Article  PubMed  Google Scholar 

  33. Cunningham C, Sanderson DJ. Malaise in the water maze: untangling the effects of LPS and IL-1beta on learning and memory. Brain Behav Immun 2008, 22: 1117–1127.

    Article  PubMed  CAS  Google Scholar 

  34. Goodwin DW, Powell B, Bremer D, Hoine H, Stern J. Alcohol and recall: state-dependent effects in man. Science 1969, 163: 1358–1360.

    Article  PubMed  CAS  Google Scholar 

  35. Rivier C, Chizzonite R, Vale W. In the mouse, the activation of the hypothalamic-pituitary-adrenal axis by a lipopolysaccharide (endotoxin) is mediated through interleukin-1. Endocrinology 1989, 125: 2800–2805.

    Article  PubMed  CAS  Google Scholar 

  36. Tilders FJ, DeRijk RH, Van Dam AM, Vincent VA, Schotanus K, Persoons JH. Activation of the hypothalamus-pituitary-adrenal axis by bacterial endotoxins: routes and intermediate signals. Psychoneuroendocrinology 1994, 19: 209–232.

    Article  PubMed  CAS  Google Scholar 

  37. Simon P, Dupuis R, Costentin J. Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions. Behav Brain Res 1994, 61: 59–64.

    CAS  Google Scholar 

  38. Treit D, Fundytus M. Thigmotaxis as a test for anxiolytic activity in rats. Pharmacol Biochem Behav 1988, 31: 959–962.

    Article  PubMed  CAS  Google Scholar 

  39. Kozak W, Conn CA, Kluger MJ. Lipopolysaccharide induces fever and depresses locomotor activity in unrestrained mice. Am J Physiol 1994, 266: R125–135.

    PubMed  CAS  Google Scholar 

  40. Goshen I, Yirmiya R. The role of pro-inflammatory cytokines in memory processes and neural plasticity. In: Ader R (Ed.), Psychoneuroimmunology. 4th ed. Elsevier AP 2007: 337–377.

  41. Pugh CR, Johnson JD, Martin D, Rudy JW, Maier SF, Watkins LR. Human immunodeficiency virus-1 coat protein gp120 impairs contextual fear conditioning: a potential role in AIDS related learning and memory impairments. Brain Res 2000, 861: 8–15.

    Article  PubMed  CAS  Google Scholar 

  42. Palin K, Bluthe RM, Verrier D, Tridon V, Dantzer R, Lestage J. Interleukin-1beta mediates the memory impairment associated with a delayed type hypersensitivity response to bacillus Calmette-Guerin in the rat hippocampus. Brain Behav Immun 2004,18: 223–230.

    Article  PubMed  CAS  Google Scholar 

  43. Pugh CR, Nguyen KT, Gonyea JL, Fleshner M, Wakins LR, Maier SF, et al. Role of interleukin-1 beta in impairment of contextual fear conditioning caused by social isolation. Behav Brain Res 1999, 106: 109–118.

    Article  PubMed  CAS  Google Scholar 

  44. Thomson LM, Sutherland RJ. Interleukin-1beta induces anorexia but not spatial learning and memory deficits in the rat. Behav Brain Res 2006, 170: 302–307.

    Article  PubMed  CAS  Google Scholar 

  45. Thomson LM, Sutherland RJ. Systemic administration of lipopolysaccharide and interleukin-1beta have different effects on memory consolidation. Brain Res Bull 2005, 67: 24–29.

    Article  PubMed  CAS  Google Scholar 

  46. Matsumoto Y, Yoshida M, Watanabe S, Yamamoto T. Involvement of cholinergic and glutamatergic functions in working memory impairment induced by interleukin-1beta in rats. Eur J Pharmacol 2001, 430: 283–288.

    Article  PubMed  CAS  Google Scholar 

  47. Oitzl MS, van Oers H, Schobitz B, de Kloet ER. Interleukin-1 beta, but not interleukin-6, impairs spatial navigation learning. Brain Res 1993, 613: 160–163.

    Article  PubMed  CAS  Google Scholar 

  48. Gibertini M. Cytokines and cognitive behavior. Neuroimmunomodulation 1998, 5: 160–165.

    Article  PubMed  CAS  Google Scholar 

  49. Barrientos RM, Higgins EA, Sprunger DB, Watkins LR, Rudy JW, Maier SF. Memory for context is impaired by a post context exposure injection of interleukin-1 beta into dorsal hippocampus. Behav Brain Res 2002, 134: 291–298.

    Article  PubMed  CAS  Google Scholar 

  50. Barrientos RM, Higgins EA, Biedenkapp JC, Sprunger DB, Wright-Hardesty KJ, Watkins LR, et al. Peripheral infection and aging interact to impair hippocampal memory consolidation. Neurobiol Aging 2006, 27: 723–732.

    Article  PubMed  Google Scholar 

  51. Barrientos RM, Frank MG, Hein AM, Higgins EA, Watkins LR, Rudy JW, et al. Time course of hippocampal IL-1 beta and memory consolidation impairments in aging rats following peripheral infection. Brain Behav Immun 2009, 23: 46–54.

    Article  PubMed  CAS  Google Scholar 

  52. Pugh CR, Fleshner M, Watkins LR, Maier SF, Rudy JW. The immune system and memory consolidation: a role for the cytokine IL-1beta. Neurosci Biobehav Rev 2001, 25: 29–41.

    Article  Google Scholar 

  53. Jarrard LE. Selective hippocampal lesions: differential effects on performance by rats of a spatial task with preoperative versus postoperative training. J Comp Physiol Psychol 1978, 92: 1119–1127.

    Article  PubMed  CAS  Google Scholar 

  54. Morris RG, Garrud P, Rawlins JN, O’Keefe J. Place navigation impaired in rats with hippocampal lesions. Nature 1982, 297: 681–683.

    Article  PubMed  CAS  Google Scholar 

  55. Moser MB, Moser EI. Distributed encoding and retrieval of spatial memory in the hippocampus. J Neurosci 1998, 18: 7535–7542.

    PubMed  CAS  Google Scholar 

  56. Riedel G, Micheau J, Lam AG, Roloff EL, Martin SJ, Bridge H, et al. Reversible neural inactivation reveals hippocampal participation in several memory processes. Nat Neurosci 1999, 2: 898–905.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Key Laboratory of Regenerative Biology, South China Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China

    Zhen-Bo Huang  (黄振波), Hao Wang  (王皓), Xiu-Rong Rao  (饶秀茸), Tao Liang  (梁涛), Jing Xu  (许晶), Xiang-Sheng Cai  (蔡祥胜) & Guo-Qing Sheng  (盛国庆)

Authors
  1. Zhen-Bo Huang  (黄振波)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hao Wang  (王皓)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiu-Rong Rao  (饶秀茸)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tao Liang  (梁涛)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jing Xu  (许晶)
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiang-Sheng Cai  (蔡祥胜)
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guo-Qing Sheng  (盛国庆)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guo-Qing Sheng  (盛国庆).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, ZB., Wang, H., Rao, XR. et al. Effects of immune activation on the retrieval of spatial memory. Neurosci. Bull. 26, 355–364 (2010). https://doi.org/10.1007/s12264-010-0622-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12264-010-0622-z

Keywords

关键词

Search

Navigation