Prolonged Periods of Social Isolation From Weaning Reduce the Anti-inflammatory Cytokine IL-10 in Blood and Brain
Life stressors during critical periods are reported to trigger an immune dysfunction characterised by abnormal production of inflammatory cytokines. Despite the relationship between early stressors and schizophrenia is described, the evidence on inflammatory biomarkers remains limited. We aimed to i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.01011/full |
| _version_ | 1818852449642872832 |
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| author | Fabiana Corsi-Zuelli Helene Aparecida Fachim Helene Aparecida Fachim Camila Marcelino Loureiro Rosana Shuhama Giuliana Bertozi Sâmia Regiane Lourenço Joca Sâmia Regiane Lourenço Joca Paulo Rossi Menezes Paulo Louzada-Junior Cristina Marta Del-Ben |
| author_facet | Fabiana Corsi-Zuelli Helene Aparecida Fachim Helene Aparecida Fachim Camila Marcelino Loureiro Rosana Shuhama Giuliana Bertozi Sâmia Regiane Lourenço Joca Sâmia Regiane Lourenço Joca Paulo Rossi Menezes Paulo Louzada-Junior Cristina Marta Del-Ben |
| author_sort | Fabiana Corsi-Zuelli |
| collection | DOAJ |
| description | Life stressors during critical periods are reported to trigger an immune dysfunction characterised by abnormal production of inflammatory cytokines. Despite the relationship between early stressors and schizophrenia is described, the evidence on inflammatory biomarkers remains limited. We aimed to investigate whether an imbalance between pro- and anti-inflammatory cytokines in the brain is reflected in the peripheral blood of rats submitted to post-weaning social isolation (pwSI), a model with validity to study schizophrenia. We evaluated pro- and anti-inflammatory cytokines (IL-6, TNF-α, and IL-10) simultaneously at blood, prefrontal cortex and hippocampal tissues (Milliplex MAP), including the respective cytokines gene expression (mRNA) (qRT-PCR TaqMan mastermix). We also performed a correlation matrix to explore significant correlations among cytokines (protein and mRNA) in blood and brain, as well as cytokines and total number of square crossings in the open field for isolated-reared animals. Male Wistar rats (n = 10/group) were kept isolated (n = 1/cage) or grouped (n = 3–4/cage) since weaning for 10 weeks. After this period, rats were assessed for locomotion and sacrificed for blood and brain cytokines measurements. Prolonged pwSI decreased IL-10 protein and mRNA in the blood, and IL-10 protein in the hippocampus, along with decreased IL-6 and its mRNA expression in the prefrontal cortex. Our results also showed that cytokines tend to correlate to one-another among the compartments investigated, although blood and brain correlations are far from perfect. IL-10 hippocampal levels were negatively correlated with hyperlocomotion in the open field. Despite the unexpected decrease in IL-6 and unchanged TNF-α levels contrast to the expected pro-inflammatory phenotype, this may suggest that reduced anti-inflammatory signalling may be critical for eliciting abnormal behaviour in adulthood. Altogether, these results suggest that prolonged early-life adverse events reduce the ability to build proper anti-inflammatory cytokine that is translated from blood-to-brain. |
| first_indexed | 2024-12-19T07:21:06Z |
| format | Article |
| id | doaj.art-fde89710c9d6494b97f60049abd3f4d4 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-19T07:21:06Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-fde89710c9d6494b97f60049abd3f4d42022-12-21T20:30:57ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-01-011210.3389/fnins.2018.01011427182Prolonged Periods of Social Isolation From Weaning Reduce the Anti-inflammatory Cytokine IL-10 in Blood and BrainFabiana Corsi-Zuelli0Helene Aparecida Fachim1Helene Aparecida Fachim2Camila Marcelino Loureiro3Rosana Shuhama4Giuliana Bertozi5Sâmia Regiane Lourenço Joca6Sâmia Regiane Lourenço Joca7Paulo Rossi Menezes8Paulo Louzada-Junior9Cristina Marta Del-Ben10Division of Psychiatry, Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilDivision of Psychiatry, Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilBiomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, United KingdomDivision of Clinical Immunology, Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilDivision of Psychiatry, Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilDepartment of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilDepartment of Physics and Chemistry, School of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, BrazilDepartment of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Aarhus, DenmarkDepartment of Preventive Medicine, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilDivision of Clinical Immunology, Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilDivision of Psychiatry, Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, BrazilLife stressors during critical periods are reported to trigger an immune dysfunction characterised by abnormal production of inflammatory cytokines. Despite the relationship between early stressors and schizophrenia is described, the evidence on inflammatory biomarkers remains limited. We aimed to investigate whether an imbalance between pro- and anti-inflammatory cytokines in the brain is reflected in the peripheral blood of rats submitted to post-weaning social isolation (pwSI), a model with validity to study schizophrenia. We evaluated pro- and anti-inflammatory cytokines (IL-6, TNF-α, and IL-10) simultaneously at blood, prefrontal cortex and hippocampal tissues (Milliplex MAP), including the respective cytokines gene expression (mRNA) (qRT-PCR TaqMan mastermix). We also performed a correlation matrix to explore significant correlations among cytokines (protein and mRNA) in blood and brain, as well as cytokines and total number of square crossings in the open field for isolated-reared animals. Male Wistar rats (n = 10/group) were kept isolated (n = 1/cage) or grouped (n = 3–4/cage) since weaning for 10 weeks. After this period, rats were assessed for locomotion and sacrificed for blood and brain cytokines measurements. Prolonged pwSI decreased IL-10 protein and mRNA in the blood, and IL-10 protein in the hippocampus, along with decreased IL-6 and its mRNA expression in the prefrontal cortex. Our results also showed that cytokines tend to correlate to one-another among the compartments investigated, although blood and brain correlations are far from perfect. IL-10 hippocampal levels were negatively correlated with hyperlocomotion in the open field. Despite the unexpected decrease in IL-6 and unchanged TNF-α levels contrast to the expected pro-inflammatory phenotype, this may suggest that reduced anti-inflammatory signalling may be critical for eliciting abnormal behaviour in adulthood. Altogether, these results suggest that prolonged early-life adverse events reduce the ability to build proper anti-inflammatory cytokine that is translated from blood-to-brain.https://www.frontiersin.org/article/10.3389/fnins.2018.01011/fullanti-inflammatory cytokinesearly stresscytokinesinflammationinterleukin-10post-weaning social isolation |
| spellingShingle | Fabiana Corsi-Zuelli Helene Aparecida Fachim Helene Aparecida Fachim Camila Marcelino Loureiro Rosana Shuhama Giuliana Bertozi Sâmia Regiane Lourenço Joca Sâmia Regiane Lourenço Joca Paulo Rossi Menezes Paulo Louzada-Junior Cristina Marta Del-Ben Prolonged Periods of Social Isolation From Weaning Reduce the Anti-inflammatory Cytokine IL-10 in Blood and Brain Frontiers in Neuroscience anti-inflammatory cytokines early stress cytokines inflammation interleukin-10 post-weaning social isolation |
| title | Prolonged Periods of Social Isolation From Weaning Reduce the Anti-inflammatory Cytokine IL-10 in Blood and Brain |
| title_full | Prolonged Periods of Social Isolation From Weaning Reduce the Anti-inflammatory Cytokine IL-10 in Blood and Brain |
| title_fullStr | Prolonged Periods of Social Isolation From Weaning Reduce the Anti-inflammatory Cytokine IL-10 in Blood and Brain |
| title_full_unstemmed | Prolonged Periods of Social Isolation From Weaning Reduce the Anti-inflammatory Cytokine IL-10 in Blood and Brain |
| title_short | Prolonged Periods of Social Isolation From Weaning Reduce the Anti-inflammatory Cytokine IL-10 in Blood and Brain |
| title_sort | prolonged periods of social isolation from weaning reduce the anti inflammatory cytokine il 10 in blood and brain |
| topic | anti-inflammatory cytokines early stress cytokines inflammation interleukin-10 post-weaning social isolation |
| url | https://www.frontiersin.org/article/10.3389/fnins.2018.01011/full |
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