Abstract

BackgroundThe CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor implicated in the control of proliferation, differentiation, and inflammatory processes mainly in adipose tissue and liver; although more recent results have revealed an important role for this transcription factor in the brain. Previous studies from our laboratory indicated that CCAAT/enhancer-binding protein β is implicated in inflammatory process and brain injury, since mice lacking this gene were less susceptible to kainic acid-induced injury. More recently, we have shown that the complement component 3 gene (C3) is a downstream target of CCAAT/enhancer-binding protein β and it could be a mediator of the proinflammatory effects of this transcription factor in neural cells.MethodsAdult male Wistar rats (8–12 weeks old) were used throughout the study. C/EBPβ+/+ and C/EBPβ–/– mice were generated from heterozygous breeding pairs. Animals were injected or not with kainic acid, brains removed, and brain slices containing the hippocampus analyzed for the expression of both CCAAT/enhancer-binding protein β and C3.ResultsIn the present work, we have further extended these studies and show that CCAAT/enhancer-binding protein β and C3 co-express in the CA1 and CA3 regions of the hippocampus after an excitotoxic injury. Studies using CCAAT/enhancer-binding protein β knockout mice demonstrate a marked reduction in C3 expression after kainic acid injection in these animals, suggesting that indeed this protein is regulated by C/EBPβ in the hippocampus in vivo.ConclusionsAltogether these results suggest that CCAAT/enhancer-binding protein β could regulate brain disorders, in which excitotoxic and inflammatory processes are involved, at least in part through the direct regulation of C3.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0742-0) contains supplementary material, which is available to authorized users.

Highlights

  • The CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor implicated in the control of proliferation, differentiation, and inflammatory processes mainly in adipose tissue and liver; more recent results have revealed an important role for this transcription factor in the brain

  • Taking into account the previous results from our laboratory showing a direct regulation of component 3 gene (C3) by C/EBPβ in neural cells [54], here we examined the possible regulation by C/EBPβ of C3 expression in the hippocampus in an animal model of excitotoxicity

  • kainic acid (KA) induces the expression of C/EBPβ and C3 genes in the hippocampus of adult rats We studied the content of C/EBPβ and C3 proteins, by immunohistochemistry analysis, in consecutive slices of the hippocampus of adult rats after KA injury

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Summary

Introduction

The CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor implicated in the control of proliferation, differentiation, and inflammatory processes mainly in adipose tissue and liver; more recent results have revealed an important role for this transcription factor in the brain. Previous studies from our laboratory indicated that CCAAT/enhancer-binding protein β is implicated in inflammatory process and brain injury, since mice lacking this gene were less susceptible to kainic acid-induced injury. Due to its relevance in the Hernandez-Encinas et al Journal of Neuroinflammation (2016) 13:276 indicated cellular processes, C/EBPβ is involved in the pathogenesis of different diseases, e.g., cancer, hyper-inflammatory processes, and bacterial infections [1, 18, 19] As it happens in normal physiological conditions, this regulation takes place via the regulation of many genes involved in these processes [15,16,17, 20, 21]

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