Cytokine pathway disruption in a mouse model of schizophrenia induced by Munc18-1a overexpression in the brain
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Gil-Pisa et al. Journal of Neuroinflammation 2014, 11:128 http://www.jneuroinflammation.com/content/11/1/128
RESEARCH
Open Access
Cytokine pathway disruption in a mouse model of schizophrenia induced by Munc18-1a overexpression in the brain Itziar Gil-Pisa1,2,3*, Carolina Cebrián1, Jorge E Ortega2,3,4, J Javier Meana2,3,4 and David Sulzer1
Abstract Background: An accumulating body of evidence points to the significance of neuroinflammation and immunogenetics in schizophrenia, and an imbalance of cytokines in the central nervous system (CNS) has been suggested to be associated with the disorder. Munc18-overexpressing mice (Munc18-OE) have provided a model for the study of the alterations that may underlie the symptoms of subjects with schizophrenia. The aim of the present study was to elucidate the involvement of neuroinflammation and cytokine imbalance in this model. Methods: Cytokines were evaluated in the cortex and the striatum of Munc18-OE and wild-type (WT) mice by enzyme-linked immunosorbent assay (ELISA). Protein levels of specific microglia and macrophage, astrocytic and neuroinflammation markers were quantified by western blot in the cortex and the striatum of Munc18-OE and WT mice. Results: Each cytokine evaluated (Interferon-gamma (IFN-γ), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-2 (IL-2) and CCL2 chemokine) was present at higher levels in the striatum of Munc18-OE mice than WT. Cortical TNF-α and IL-2 levels were significantly lower in Munc18-OE mice than WT mice. The microglia and macrophage marker CD11b was lower in the cortexes of Munc18-OE mice than WT, but no differences were observed in the striatum. Glial Fibrillary Acidic Protein (GFAP) and Nuclear Factor-kappaB (NF-κB)p65 levels were not different between the groups. Interleukin-1beta (IL-1β) and IL-6 levels were beneath detection limits. Conclusions: The disrupted levels of cytokines detected in the brain of Munc18-OE mice was found to be similar to clinical reports and endorses study of this type for analysis of this aspect of the disorder. The lower CD11b expression in the cortex but not in the striatum of the Munc18-OE mice may reflect differences in physiological activity. The cytokine expression pattern observed in Munc18-OE mice is similar to a previously published model of schizophrenia caused by maternal immune activation. Together, these data suggest a possible role for an immune imbalance in this disorder. Keywords: Munc18-1a, Animal model, Schizophrenia, Neuroinflammation, Cytokine
Background Inflammation is a complex response of the host to tissue injury such as an infection or a physical insult [1]. Cytokines are a family of proteins that mediate host response to infection, and are considered to be markers of infectious and inflammatory conditions [2,3]. Cytokines further * Correspondence: [email protected] 1 Department of Neurology, Columbia University Medical Center, 710 W, 168th Street, New York, NY 10032, USA 2 Department of Pharmacology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa, Bizk
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