Increased Levels of C1q in the Prefrontal Cortex of Adult Offspring after Maternal Immune Activation: Prevention by 7,8-Dihydroxyflavone
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Objective: Prenatal infection is implicated in the etiology of schizophrenia. The objective of this paper is to study the role of complement protein C1q in the psychosis of adult offspring after maternal immune activation (MIA). In addition, effect of 7,8-dihydroxyflavone (7,8-DHF: a tropomyosin receptor kinase B [TrkB] agonist) was also examined. Methods: Western blot analysis of C1q in the brain regions from adult offspring after prenatal poly(I:C) (5.0 mg/kg/day from E12 to E17) exposure was performed. 7,8-DHF or vehicle was given from 4 to 8-weeks old. Results: Expression of C1q in the prefrontal cortex (PFC) of adult offspring from poly(I:C)-treated pregnant mice was significantly higher than that of control group. Early treatment with 7,8-DHF during juvenile and adolescent stages could prevent an increase of C1q in the PFC of adult offspring after MIA. Conclusion: Therefore, it is likely that increased C1q expression in the frontal cortex may play a role in the behavioral abnormalities of adult offspring after MIA. Furthermore, supplementation with a TrkB agonist such as 7,8-DHF during the prodromal stage may have prophylactic effects on the behavioral abnormalities after MIA.
Abstract
Objective: Prenatal infection is implicated in the etiology of schizophrenia. The objective of this paper is to study the role of complement protein C1q in the psychosis of adult offspring after maternal immune activation (MIA). In addition, effect of 7,8-dihydroxyflavone (7,8-DHF: a tropomyosin receptor kinase B [TrkB] agonist) was also examined. Methods: Western blot analysis of C1q in the brain regions from adult offspring after prenatal poly(I:C) (5.0 mg/kg/day from E12 to E17) exposure was performed. 7,8-DHF or vehicle was given from 4 to 8-weeks old. Results: Expression of C1q in the prefrontal cortex (PFC) of adult offspring from poly(I:C)-treated pregnant mice was significantly higher than that of control group. Early treatment with 7,8-DHF during juvenile and adolescent stages could prevent an increase of C1q in the PFC of adult offspring after MIA. Conclusion: Therefore, it is likely that increased C1q expression in the frontal cortex may play a role in the behavioral abnormalities of adult offspring after MIA. Furthermore, supplementation with a TrkB agonist such as 7,8-DHF during the prodromal stage may have prophylactic effects on the behavioral abnormalities after MIA.
참고문헌 (14)
- Sullivan PF, "The genetics of schizophrenia", PLoS Med, 2, pp.e212~ (2005)
- Brown AS, "Prenatal infection and schizophrenia : a review of epidemiologic and translational studies", Am J Psychiatry, 167, pp.261~280 (2010)
- Meyer U, "Neural basis of psychosis-related behaviour in the infection model of schizophrenia", Behav Brain Res, 204, pp.322~334 (2009)
- Knuesel I, "Maternal immune activation and abnormal brain development across CNS disorders", Nat Rev Neurol, 10, pp.643~660 (2014)
- Agarwal V, "Roles of complement C1q in pneumococcus-host interactions", Crit Rev Immunol, 35, pp.173~184 (2015)
- Kouser L, "Emerging and novel functions of complement protein C1q", Front Immunol, 6, pp.317~ (2015)
- Severance EG, "Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia", Neurobiol Dis, 48, pp.447~453 (2012)
- Severance EG, "Maternal complement C1q and increased odds for psychosis in adult offspring", Schizophr Res, 159, pp.14~19 (2014)
- Han M, "Intake of 7,8-dihydroxyflavone during juvenile and adolescent stages prevents onset of psychosis in adult offspring after maternal immune activation", Sci Rep, 6, pp.36087~ (2016)
- Jang SW, "A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone", Proc Natl Acad Sci U S A, 107, pp.2687~2692 (2010)
- Zhang JC, "Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation", Int J Neuropsychopharmacol, 18, pp.pyu077~ (2014)
- Ozawa K, "Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring : a neurodevelopmental animal model of schizophrenia", Biol Psychiatry, 59, pp.546~554 (2006)
- Arakelyan A, "Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia", BMC Clin Pathol, 11, pp.10~ (2011)
- Miller BJ, "Towards an immunophenotype of schizophrenia: progress, potential mechanisms, and future directions", Neuropsychopharmacology, 42, pp.299~317 (2016)