Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-05T19:54:27.182Z Has data issue: false hasContentIssue false
  • English
  • Français

Involvement of NLRP3 inflammasome in schizophrenia-like behaviour in young animals after maternal immune activation

Published online by Cambridge University Press:  14 July 2020

Letícia Ventura ,
Viviane Freiberger ,
Vinicius B. Thiesen ,
Paula Dias ,
Matheus L. Dutra ,
Bruna B. Silva ,
Aline D. Schlindwein  and
Clarissa M. Comim Open the ORCID record for Clarissa M. Comim [Opens in a new window]
Letícia Ventura
Affiliation:
Research Group in Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, University of South Santa Catarina, Avenida Pedra Branca, 25, Pedra Branca, 88137-270Palhoça, SC, Brazil
Viviane Freiberger
Affiliation:
Research Group in Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, University of South Santa Catarina, Avenida Pedra Branca, 25, Pedra Branca, 88137-270Palhoça, SC, Brazil
Vinicius B. Thiesen
Affiliation:
Research Group in Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, University of South Santa Catarina, Avenida Pedra Branca, 25, Pedra Branca, 88137-270Palhoça, SC, Brazil
Paula Dias
Affiliation:
Research Group in Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, University of South Santa Catarina, Avenida Pedra Branca, 25, Pedra Branca, 88137-270Palhoça, SC, Brazil
Matheus L. Dutra
Affiliation:
Research Group in Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, University of South Santa Catarina, Avenida Pedra Branca, 25, Pedra Branca, 88137-270Palhoça, SC, Brazil
Bruna B. Silva
Affiliation:
Research Group on Allergy, Inflammation and Infectious Disease, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, University of South Santa Catarina, Avenida Pedra Branca, 25, Pedra Branca, 88137-270Palhoça, SC, Brazil
Aline D. Schlindwein
Affiliation:
Research Group on Allergy, Inflammation and Infectious Disease, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, University of South Santa Catarina, Avenida Pedra Branca, 25, Pedra Branca, 88137-270Palhoça, SC, Brazil
Clarissa M. Comim*
Affiliation:
Research Group in Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, University of South Santa Catarina, Avenida Pedra Branca, 25, Pedra Branca, 88137-270Palhoça, SC, Brazil
*
Author for correspondence: Clarissa M. Comim, Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

To evaluate the involvement of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in schizophrenia-like behaviour in young animals exposed to maternal immune activation (MIA).

Methods:

To this aim, on the 15th gestational day, the females received an injection of lipopolysaccharides. When the animals completed 7, 14 and 45 postnatal days, they were killed and the whole brain was dissected for biochemical analysis. Animals with 45 postnatal days were submitted to behavioural tests of locomotor activity, social interaction and stereotyped movements.

Results:

It was observed that the animals presented schizophrenia-like behaviour at 45 postnatal days associated with the increase of NLRP3 inflammasome expression and IL-1β levels on 7, 14 and 45 postnatal days.

Conclusion:

This study shows that MIA may be associated with a schizophrenia-like behaviour. This behaviour can be induced to a neuroinflammatory profile in the brain. These evidences may base future studies on the relationship between neuroinflammation and psychiatric disorders.

Keywords

maternal immune activationNLRP3 inflammasomeIL-1β levelsschizophrenia-like behaviour
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 32 , Issue 6 , December 2020 , pp. 321 - 327
Copyright
© Scandinavian College of Neuropsychopharmacology 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alcocer-Gómez, E, Casas-Barquero, N, Williams, MR, Romero-Guillena, SL, Cañadas-Lozano, D, Bullón, P, Sánchez-Alcazar, JA, Navarro-Pando, JM and Cordero, MD (2017) Antidepressants induce autophagy dependent-NLRP3-inflammasome inhibition in major depressive disorder. Pharmacological Research 121, 114–121.CrossRefGoogle ScholarPubMed
Antonelli, MC (2015) Perinatal Programming of Neurodevelopment. New York, NY: Springer.CrossRefGoogle Scholar
Ashdown, H, Dumont, Y, Ng, M, Poole, S, Boksa, P and Luheshi, GN (2006) The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia. Molecular Psychiatry 11(1), 47–55.CrossRefGoogle Scholar
Ayhan, Y, McFarland, R and Pletnikov, MV (2016) Animal models of gene-environment interaction in schizophrenia: a dimensional perspective. Progress in Neurobiology 136(2), 1–27.CrossRefGoogle ScholarPubMed
Bale, TL (2001) Sex differences in prenatal epigenetic programming of stress pathways. Stress 14(1), 348–356.CrossRefGoogle Scholar
Baharnoori, M, Bhardwaj, SK and Srivastava, LK (2012) Neonatal behavioral changes in rats with gestational exposure to lipopolysaccharide: a prenatal infection model for developmental neuropsychiatric disorders. Schizophrenia Bulletin 38(1), 444–456.CrossRefGoogle ScholarPubMed
Bauernfeind, FG, Horvath, G, Stutz, A, Alnemri, ES, MacDonald, K, Speert, D, Fernandes-Alnemri, T., Wu, J, Monks, BG, Fitzgerald, KA, Hornung, V and Latz, E (2009) Cutting edge: NF-κB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. Journal of Immunology 183(1), 787–791.CrossRefGoogle ScholarPubMed
Bauman, MD, Iosif, AM, Smith, SEP, Bregere, C, Amaral, DG and Patterson, PH (2014) Activation of the maternal immune system during pregnancy alters behavioral development of rhesus monkey offspring. Biol. Psychiatry 75(1), 332–341.CrossRefGoogle ScholarPubMed
Borrell, J, Vela, JM, Arevalo-Martin, A, Molina-Holgado, E and Guaza, C (2002) Prenatal immune challenge disrupts sensorimotor gating in adult rats. Implications for the Etiopathogenesis of Schizophrenia Neuropsychopharmacology 26(1), 204–215.Google ScholarPubMed
Boksa, P (2010) Effects of prenatal infection on brain development and behavior: a review of findings from animal models. Brain, Behavior, and Immunity 24(1), 881–97.CrossRefGoogle ScholarPubMed
Brown, AS, Begg, MD, Gravenstein, S, Schaefer, CA, Wyatt, RJ and Bresnahan, M (2004) Serologic-evidence of pré natal influenza in the etiology of schizophrenia. Archives of General Psychiatry 61(1), 774–780.CrossRefGoogle Scholar
Buka, SL, Tsuang, MT, Torrey, EF, Klebanoff, MA, Bernstein, D and Yolken, RH (2001) Maternal infections and subsequent psychosis among offspring. Archives of General Psychiatry 58(1), 1032–1037.CrossRefGoogle ScholarPubMed
Cohen, M, Solowij, N and Carr, V (2008) Cannabis, cannabinoids, and schizophrenia: integration of the evidence. Australian and New Zealand Journal of Psychiatry 42(1), 357–368.CrossRefGoogle Scholar
Coll, RC, Robertson, AA, Chae, JJ, Higgins, SC, Munoz-Planillo, R, Inserra, MC, Vetter, I, Dungan, LS, Monks, BG, Stutz, A, Croker, DE, Butler, MS, Haneklaus, M, Sutton, CE, Núñez, G, Latz, E, Kastner, DL, Mills, KHG, Masters, SL, Schroder, K, Cooper, MA and O’Neill, LAJ (2015) A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nature Medicine 21(1), 248–255.CrossRefGoogle ScholarPubMed
Compan, V, Baroja-Mazo, A, López-Castejón, G, Gomez, AI, Martínez, CM, Angosto, D, Montero, MT, Herranz, AS, Bazán, E, Reimers, D, Mulero, V and Pelegrín, P (2012) Cell volume regulation modulates NLRP3 inflammasome activation. Immunity 37(1), 487–500.CrossRefGoogle ScholarPubMed
Cuesta, MJ, Sanchez-Torres, AM, Cabrera, B, Bioque, M, Merchan-Naranjo, J and Corripio, I (2009) Premorbid adjustment and clinical correlates of cognitive impairment in first-episode psychosis. the PEPs Cog Study. Schizophrenia Research 164, 65–73.CrossRefGoogle Scholar
Cunningham, K, Stansfield, SH, Patel, P, Menon, S, Kienzle, V, Allan, JA and Huston, WM (2013) The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection. BMC Immunology 15(1), 14:50.Google Scholar
Eller, LS, Bunch, EH, Wantland, DJ, Portillo, CJ, Reynolds, NR, Nokes, KM, Coleman, CL, Kemppainen, JK, Kirksey, KM, Corless, IB, Hamilton, MJ, Dole, PJ, Nicholas, PK, Holzemer, WL and Tsai, YF (2010) Prevalence, correlates, and self-management of HIV-related depressive symptoms. AIDS Care 22(3), 1159–1170.CrossRefGoogle ScholarPubMed
Faro, S and Fenner, DE (1998) Urinary tract infections. Clinical Obstetrics and Gynecology 4(2), 744–754.CrossRefGoogle Scholar
File, SE and Seth, P (2003) A review of 25 years of the social interaction test. European Journal of Pharmacology 463(2), 35–53.CrossRefGoogle ScholarPubMed
Fineberg, AM and Ellman, LM (2013) Review inflammatory cytokines and neurological and neurocognitive alterations in the course of schizophrenia. Biological Psychiatry 73(1), 951–966.CrossRefGoogle ScholarPubMed
Fortier, ME, Joober, R, Luheshi, GN and Boksa, P (2004) Maternal exposure to bacterial endotoxin during pregnancy enhances amphetamine-induced locomotion and startle responses in adult rat offspring. Journal of Psychiatric Research 38(2), 335–345.CrossRefGoogle ScholarPubMed
Halle, A, Hornung, V, Petzold, GC, Stewart, CR and Monks, BG (2008) The NALP3 inflammasome is involved in the innate immune response to amyloid-β. Nature Immunology 2(1), 857–865.CrossRefGoogle Scholar
Harvey, L and Boksa, P (2012) Review prenatal and postnatal animal models of immune activation: relevance to a range of neurodevelopmental disorders. Developmental Neurobiology 72(3), 1335–1348.CrossRefGoogle ScholarPubMed
Jiang, HY, Xu, LL, Shao, L, Xia, RM, Yu, ZH, Ling, ZX, Yang, F, Deng, M and Ruan, B (2016) Maternal infection during pregnancy and risk of autism spectrum disorders: a systematic review and meta-analysis. Brain, Behavior, and Immunity 58(3), 165–172.CrossRefGoogle ScholarPubMed
Kirsten, TB, Taricano, M, Maiorka, PC, Palermo-Neto, J and Bernardi, MM (2010) Prenatal lipopolysaccharide reduces social behavior in male offspring. Neuroimmunomodulation 17(3), 240–251.CrossRefGoogle ScholarPubMed
Kim, HK, Andreazza, AC, Elmi, N, Chen, W and Young, LT (2016) Nod-Like receptor pyrin containing 3 (NLRP3) in the post-mortem frontal córtex from patients with bipolar disorder: a potential mediator between mitochondria and immune activation. Journal of Psychiatric Research 72(3), 43–50.CrossRefGoogle ScholarPubMed
Knuesel, I, Chicha, L, Britschgi, M, Schobel, SA, Bodmer, M, Hellings, JA, Toovey, S and Prinssen, EP (2014) Maternal immune activation and abnormal rain development across CNS disorders. Nature Reviews Neurology 10(3), 643–660.CrossRefGoogle Scholar
Lavelle, M, Healey, PG and McCabe, R (2014) Nonverbal behavior during face-to-face social interaction in schizophrenia: a review. The Journal of Nervous and Mental Disease 202(5), 47–54.CrossRefGoogle ScholarPubMed
Li, R, Wang, X, Qin, T, Qu, R and Ma, S (2016) Apigenin ameliorates chronic mild stress-induced depressive behavior by inhibiting interleukin-1β production and NLRP3 inflammasome activation in the rat brain. Behavioural Brain Research 296(9), 318–325.CrossRefGoogle ScholarPubMed
Maki, P, Veijola, J, Jones, PB, Murray, GK, Koponen, H, Tienari, P, Miettunen, J, Tanskanen, P, Wahlberg, K, Koskinen, J, Lauronen, E and Isohanni, M (2005) Predictors of schizophrenia – a review. British Medical Bulletin 1, 1–15.CrossRefGoogle Scholar
Mariathasan, S, Weiss, DS, Newton, K, McBride, J, O’Rourke, K, Roose-Girma, M, Lee, WP, Weinrauch, Y, Monack, DM and Dixit, VM (2006) Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440(1), 228–232.CrossRefGoogle ScholarPubMed
Martinon, F, Mayor, A and Tschopp, J (2009) The inflammasomes: guardians of the body. Annual Review of Immunology 27(2), 229–65.CrossRefGoogle Scholar
Meyer, U (2013) Developmental neuroinflammation and schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry 42(3), 20–34.CrossRefGoogle Scholar
Meyer, U and Feldon, J (2010) Epidemiology-driven neurodevelopmental animal models of schizophrenia. Progress in Neurobiology 90(1), 285–326.CrossRefGoogle ScholarPubMed
Meyer, U (2014) Prenatal poly(i:C) exposure and other developmental immune activation models in rodent systems. Biological Psychiatry 75(1), 307–315 CrossRefGoogle Scholar
Meyer, U, Murray, PJ, Urwyler, A, Yee, BK, Schedlowsk, M and Feldon, J (2008) Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10 mediated anti-inflammatory signaling. Molecular Psychiatry 13(1), 208–221.CrossRefGoogle ScholarPubMed
Miller, BJ, Culpepper, N, Rapaport, MH and Buckley, P (2013) Prenatal inflammation and neurodevelopment in schizophrenia: a review of human studies. Progress in Neuro-Psychopharmacology & Biological Psychiatry 1, 42.Google Scholar
Murray, RM, Bhavsar, V, Tripoli, G and Howes, O (2017) 30 years on: how the neurodevelopmental hypothesis of schizophrenia morphed into the developmental risk factor model of psychosis. Schizophrenia Bulletin 21, 1190–1196.CrossRefGoogle Scholar
Pan, Y, Chen, XY, Zhang, QY and Kong, LD (2014) Microglial NLRP3 inflammasome activation mediates IL-1β-related inflammation in prefrontal cortex of depressive rats. Brain, Behavior, and Immunity 41, 90–100.CrossRefGoogle ScholarPubMed
Parboosing, R, Bao, Y, Shen, L, Schaefer, CA and Brown, AS (2013) Gestational influenza and bipolar disorder in adult offspring. JAMA Psychiatry 70, 677–85.CrossRefGoogle ScholarPubMed
Pétrilli, V, Dostert, C, Muruve, DA and Tschopp, J (2007) The inflammasome: a danger sensing complex triggering innate immunity. Current Opinion in Immunology 19, 615–22.CrossRefGoogle ScholarPubMed
Ramos, HJ, Lanteri, MC, Blahnik, G, Negash, A, Suthar, MS, Brassil, MM, Sodhi, K, Treuting, PM, Busch, MP, Norris, PJ and Gale, M Jr (2012) IL-1β signaling promotes CNS-intrinsic immune control of West Nile virus infection. PLOS Pathogens 8, e1003039.CrossRefGoogle ScholarPubMed
Ratnayake, U, Quinn, T, Walker, DW and Dickinson, H (2013) Cytokines and the neurodevelopmental basis of mental illness. Frontiers in Neuroscience 7, 1–9.CrossRefGoogle ScholarPubMed
Scola, G and Duong, A (2017) Prenatal maternal immune activation and brain development with relevance to psychiatric disorders. Neuroscience 346, 403–408.CrossRefGoogle ScholarPubMed
Smith, SEP, Li, J, Garbett, K, Mirnics, K and Patterson, PH (2007) Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci 27, 10695–10702.CrossRefGoogle ScholarPubMed
Sui, YH, Luo, WJ, Xu, QY and Hua, J (2016) Dietary saturated fatty acid and polyunsaturated fatty acid oppositely affect hepatic NOD-like receptor protein 3 inflammasome through regulating nuclear factor-kappa b activation. World Journal of Gastroenterology 22, 2533–2544.CrossRefGoogle ScholarPubMed
Tanaka, S, Ide, M and Shibutani, T (2006) Spinal AMPA receptor inhibition attenuates mechanical allodynia and neuronal hyperexcitability following spinal cord injury in rats. Journal of Neuroscience Research 83, 557–566.CrossRefGoogle Scholar
Taylor, PV, Veenema, AH, Paul, MJ, Bredewold, R, Isaacs, S and de Vries, GJ (2012) Sexually dimorphic effects of a prenatal immune challenge on social play and vasopressin expression in juvenile rats. Biology of Sex Differences 1, 14–15.Google Scholar
Thornberry, NA, Bull, HG, Calaycay, JR, Chapman, KT, Howard, AD, Kostura, MJ, Miller, DK, Molineaux, SM, Weidner, JR and Aunins, J (1992) A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356, 768–774.CrossRefGoogle ScholarPubMed
Trépanier, MO, Hopperton, KE, Mizrahi, R, Mechawar, N and Bazinet, RP (2016) Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review. Molecular Psychiatry 21, 1009–26.CrossRefGoogle ScholarPubMed
Uhlhaas, PJ and Singer, W (2010) Abnormal neural oscillations and synchrony in schizophrenia. Nature Reviews Neuroscience 11, 100–13.CrossRefGoogle Scholar
Weir, RK, Forghany, R and Smith, SEP (2015) Preliminary evidence of neuropathology in nonhuman primates prenatally exposed to maternal immune activation. Brain, Behavior, and Immunity 48, 139–146.CrossRefGoogle ScholarPubMed
World Health Organization (2019). SuicideGoogle Scholar
Zhang, Y, Cazakoff, BN, Thai, CA and Howland, JG (2012) Prenatal exposure to a viral mimetic alters behavioural flexibility in male, but not female, rats. Neuropharmacology 62, 1299–1307.CrossRefGoogle Scholar
Zhu, W, Cao, FS, Feng, J, Chen, HW, Wan, JR, Lu, Q and Wang, J (2017) NLRP3 inflammasome activation contributes to long-term behavioral alterations in mice injected with lipopolysaccharide. Neuroscience 343, 77–84.CrossRefGoogle ScholarPubMed
Zuckerman, L and Weiner, I (2005) Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring. Journal of Psychiatric Research 39, 311–323.CrossRefGoogle ScholarPubMed