The role of neuroinflammation in cognitive functions and social interaction in mice with age-dependent neurodegeneration

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Abstract

Introduction. Early activation of the innate immune response as a compensatory mechanism can lead to the damage of vessels and their dysfunction. This enables the development and progression of cognitive dysfunction, alteration of cerebral microcirculation, thus makes the onset of age-related neurodegenerative diseases possible. Inflammasomes of NLRP3 play the important role as far as they are triggers of the inflammatory process in age-related chronic neurodegenerative diseases.

Objectives. To study the development of social and cognitive impairments in aging NLRP3 knockout animals.

Material and methods. The experimental group was NLRP3 knockout (NLRP3-/-) male mice of the line B6.129S6-Nlrp3tm1Bhk / JJ) aged 12 months (n=10); control group – C57BL/6.SJL male mice aged 12 months (n=10). Neurobehavioral testing: “open field” test, “X-maze” test, “light-dark box”, three-chamber social test, and “five-trial social memory” test.

Results. In the “open field” test, when the social object appeared, NLRP3-/- animals spent less time at the center of the field I in comparison with the animals of the C57BL/6 line (p=0.013). NLRP3-/- animals spent more time in the black chamber compared to the animals in the control group (p=0.037) in the “light-dark box” test. In the “three-chamber social” test NLRP3-/- animals spent the same time both with the new and the already familiar social object (p=0.885). In the “five-trial social memory” test NLRP3-/- animals did not demonstrate reduction of interest towards individuals of the opposite sex in the fourth attempt compared to the first attempt.

Conclusion. NLRP3-/- mice have the increased levels of anxiety and inhibition, disruption of memory, and destructive changes in the field of social contacts and interactions. This indicates a disorder in the sphere of emotional behavior, as well as social memory

About the authors

Yana V. Gorina

Voyno-Yasenetsky Krasnoyarsk State Medical University

Email: yana_20@bk.ru
Russian Federation, Krasnoyarsk

Olga L. Lopatina

Voyno-Yasenetsky Krasnoyarsk State Medical University

Email: yana_20@bk.ru
Russian Federation, Krasnoyarsk

Yuliya K. Komleva

Voyno-Yasenetsky Krasnoyarsk State Medical University

Email: yana_20@bk.ru
Russian Federation, Krasnoyarsk

Anatolii I. Chernikh

Krasnoyarsk City Hospital No. 20 named after I.S. Berzon

Email: yana_20@bk.ru
Russian Federation, Krasnoyarsk

Alla B. Salmina

Voyno-Yasenetsky Krasnoyarsk State Medical University

Author for correspondence.
Email: yana_20@bk.ru
Russian Federation, Krasnoyarsk

References

  1. Green D.R., Galluzzi L., Kroemer G. Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science 2011; 333(6046): 1109–1112. doi: 10.1126/science.1201940. PMID: 21868666.
  2. Lumeng C.N., Liu J., Geletka L. et al. Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue. J Immunol 2011; 187(12): 6208–6216. doi: 10.4049/jimmunol.1102188. PMID: 22075699.
  3. Venegas C., Heneka M.T. Danger-associated molecular patterns in Alzheimer’s disease. J Leukoc Biol 2017; 101(1): 87–98. doi: 10.1189/jlb.3MR0416-204R. PMID: 28049142.
  4. Heneka M.T., Carson M.J., El Khoury J. et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol 2015; 14(4): 388–405. doi: 10.1016/S1474-4422(15)70016-5. PMID: 25792098.
  5. Zotova E., Bharambe V., Cheaveau M. et al. Inflammatory components in human Alzheimer’s disease and after active amyloid-β42 immunization. Brain J Neurol 2013; 136(Pt 9): 2677–2696. doi: 10.1093/brain/awt210. PMID: 23943781.
  6. Matarin M., Salih D.A., Yasvoina M. et al. A genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology. Cell Rep 2015; 10(4): 633–44. doi: 10.1016/j.celrep.2014.12.041. PMID: 25620700.
  7. Heneka M.T. Inflammasome activation and innate immunity in Alzheimer’s disease. Brain Pathol 2017; 27(2): 220–222. doi: 10.1111/bpa.12483. PMID: 28019679.
  8. Strowig T., Henao-Mejia J., Elinav E., Flavell R. Inflammasomes in health and disease. Nature 2012; 481(7381): 278–286. doi: 10.1038/nature10759. PMID: 22258606.
  9. Ramanan V.K., Risacher S.L., Nho K. et al. GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer’s disease implicates microglial activation gene IL1RAP. Brain J Neurol 2015; 138(Pt 10): 3076–3088. doi: 10.1093/brain/awv231. PMID: 26268530.
  10. Youm Y.H., Kanneganti T.D., Vandanmagsar B. et al. The Nlrp3 inflammasome promotes age-related thymic demise and immunosenescence. Cell Rep 2012; 1(1): 56–68. doi: 10.1016/j.celrep.2011.11.005. PMID: 22832107.
  11. Vandanmagsar B., Youm Y.H., Ravussin A. et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 2011; 17(2): 179–88. doi: 10.1038/nm.2279. PMID: 21217695.
  12. Yu D., Corbett B., Yan Y. et al. Early cerebrovascular inflammation in a transgenic mouse model of Alzheimer’s disease. Neurobiol Aging 2012; 33(12): 2942–2947. doi: 10.1016/j.neurobiolaging.2012.02.023. PMID: 22440674.
  13. Merlini M., Davalos D., Akassoglou K. In vivo imaging of the neurovascular unit in CNS disease. Intravital 2012; 1(2): 87–94. doi: 10.4161/intv.22214. PMID: 25197615.
  14. Gallart-Palau X., Serra A., Lee B.S.T. et al. Brain ureido degenerative protein modifications are associated with neuroinflammation and proteinopathy in Alzheimer’s disease with cerebrovascular disease. J Neuroinflammation 2017; 14(1): 175. doi: 10.1186/s12974-017-0946-y. PMID: 28865468.
  15. Sato N., Morishita R. Roles of vascular and metabolic components in cognitive dysfunction of Alzheimer disease: short- and long-term modification by non-genetic risk factors. Front Aging Neurosci 2013; 5: 64. doi: 10.3389/fnagi.2013.00064. PMID: 24204343.
  16. Takeda S., Sato N., Morishita R. Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy. Front Aging Neurosci 2014; 6: 171. doi: 10.3389/fnagi.2014.00171. PMID: 25120476.
  17. Takeda S., Sato N., Ikimura K. et al. Increased blood-brain barrier vulnerability to systemic inflammation in an Alzheimer disease mouse model. Neurobiol Aging 2013; 34(8): 2064–2070. doi: 10.1016/j.neurobiolaging.2013.02.010. PMID: 23561508.
  18. Heneka M.T., Kummer M.P., Stutz A. et al. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature 2013; 493(7434): 674–678. doi: 10.1038/nature11729. PMID: 23254930.
  19. Weinstock M. Prenatal stressors in rodents: Effects on behavior. Neurobiol Stress 2016; 6: 3–13. doi: 10.1016/j.ynstr.2016.08.004. PMID: 28229104.
  20. Gorina Y.V., Komleva Y.K., Lopatina O.L. et al. [The battery of tests for behavioral phenotyping of aging animals in the experiment]. Adv Gerontol 2017; 30(1): 49–55. PMID: 28557390.
  21. Zhang M., Liu Y., Zhao M. et al. Depression and anxiety behaviour in a rat model of chronic migraine. J Headache Pain 2017; 18(1): 27. doi: 10.1186/s10194-017-0736-z. PMID: 28224378.
  22. Bourin M. Animal models for screening anxiolytic-like drugs: a perspective. Dialogues Clin Neurosci 2015; 17(3): 295–303. PMID: 26487810.
  23. Yang M., Silverman J.L., Crawley J.N. Automated three-chambered social approach task for mice. Curr Protoc Neurosci 2011; 8: 8.26. doi: 10.1002/0471142301.ns0826s56. PMID: 21732314.
  24. Müller L., Weinert D. Individual recognition of social rank and social memory performance depends on a functional circadian system. Behav Processes 2016; 132: 85–93. doi: 10.1016/j.beproc.2016.10.007. PMID: 27744087.
  25. Olsen I., Singhrao S.K. Inflammasome involvement in Alzheimer’s disease. J Alzheimers Dis 2016; 54(1): 45–53. doi: 10.3233/JAD-160197. PMID: 27314526.
  26. Rovira-Llopis S., Apostolova N., Bañuls C. et al. Mitochondria, the NLRP3 inflammasome, and sirtuins in type 2 diabetes: new therapeutic targets. Antioxid Redox Signal 2018. doi: 10.1089/ars.2017.7313. PMID: 29256638.
  27. Karasawa T., Takahashi M. The crystal-induced activation of NLRP3 inflammasomes in atherosclerosis. Inflamm Regen 2017; 37: 18. doi: 10.1186/s41232-017-0050-9. PMID: 29259717.
  28. Goto M. Inflammaging (inflammation + aging): A driving force for human aging based on an evolutionarily antagonistic pleiotropy theory? Biosci Trends 2008; 2(6): 218–230. PMID: 20103932.
  29. Shrestha R., Millington O., Brewer J., Bushell T. Is central nervous system an immune-privileged site? Kathmandu Univ Med J 2013; 11(41):102–107. PMID: 23774427.
  30. Quan N., Banks W.A. Brain-immune communication pathways. Brain Behav Immun 2007; 21(6): 727–735. doi: 10.1016/j.bbi.2007.05.005. PMID: 17604598.
  31. Kinnecom C., Lev M.H., Wendell L. et al. Course of cerebral amyloid angiopathy-related inflammation. Neurology 2007; 68(17): 1411–1416. doi: 10.1212/01.wnl.0000260066.98681.2e. PMID: 17452586.
  32. Koyama A., O’Brien J., Weuve J. The role of peripheral inflammatory markers in dementia and Alzheimer’s disease: a meta-analysis. J Gerontol A Biol Sci Med Sci 2013; 68(4): 433–440. doi: 10.1093/gerona/gls187. PMID: 22982688.
  33. Yang F., Wang Z., Wei X. et al. NLRP3 deficiency ameliorates neurovascular damage in experimental ischemic stroke. J Cereb Blood Flow Metab 2014; 34(4): 660–667. doi: 10.1038/jcbfm.2013.242. PMID: 24424382.
  34. Youm Y.H., Grant R.W., McCabe L.R. et al. Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging. Cell Metab 2013; 18(4): 519–532. doi: 10.1016/j.cmet.2013.09.010. PMID: 24093676.
  35. Osborn L.M., Kamphuis W., Wadman W.J., Hol E.M. Astrogliosis: an integral player in the pathogenesis of Alzheimer’s disease. Prog Neurobiol 2016; 144: 121–141. doi: 10.1016/j.pneurobio.2016.01.001. PMID: 26797041.

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Copyright (c) 2018 Gorina Y.V., Lopatina O.L., Komleva Y.K., Chernikh A.I., Salmina A.B.

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