Prolonged Periods of Social Isolation From Weaning Reduce the Anti-inflammatory Cytokine IL-10 in Blood and Brain

Author(s)

Corsi-Zuelli, Fabiana ^[1] ; Fachim, Helene Aparecida ^{[2, 1]} ; Loureiro, Camila Marcelino ^[3] ; Shuhama, Rosana ^[1] ; Bertozi, Giuliano ^[4] ; Joca, Samia Regiane Lourengo ^{[5, 6]} ; Menezes, Paulo Rossi ^[7] ; Louzada-Junior, Paulo ^[3] ; Del-Ben, Cristina Marta ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Div Psychiat, Dept Neurosci & Behav, Ribeirao Preto - Brazil

^[2] Sheffield Hallam Univ, Biomol Sci Res Ctr, Sheffield, S Yorkshire - England

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Div Clin Immunol, Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[5] Aarhus Univ, Dept Clin Med, Translat Neuropsychiat Unit, Aarhus - Denmark

^[6] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Phys & Chem, Ribeirao Preto - Brazil

^[7] Univ Sao Paulo, Fac Med, Dept Prevent Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN NEUROSCIENCE; v. 12, JAN 11 2019.
• Web of Science Citations: 1

Abstract

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-alpha, 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-alpha 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. (AU)

• FAPESP's process: 13/11167-3 - Gene-environment interactions in Schizophrenia and other psychotic disorders
• Grantee: Rosana Shuhama
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/00624-5 - DNA methylation investigation in first episode of psychosis and in rats undergoing isolation rearing from weaning in the two major excitatory and inhibitory systems
• Grantee: Helene Aparecida Fachim
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 16/12195-9 - Impact of early life stress in the inflammatory profile of first episode of psychosis (FEP) patients and in the animal model of post-weaning social isolation
• Grantee: Fabiana Maria das Graças Corsi Zuelli
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 15/02948-7 - Study of epigenetic alterations in GABAergic neurotransmission in schizophrenia and other psychoses and in animals undergoing social isolation from weaning
• Grantee: Helene Aparecida Fachim
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/17480-6 - Impact of early life stress in the inflammatory profile of first episode of psychosis (FEP) patients and in the animal model of post-weaning social isolation
• Grantee: Fabiana Maria das Graças Corsi Zuelli
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• FAPESP's process: 12/05178-0 - Schizophrenia and other psychotic disorders: social and biological determinants
• Grantee: Paulo Rossi Menezes
• Support Opportunities: Research Projects - Thematic Grants