title: Complement component 3 (C3) expression in the hippocampus after excitotoxic injury: role of C/EBPβ.
abstract: 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; 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.
  
  
  
  Adult 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.
  
  
  
  In 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.
  
  
  
  Altogether 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.
authors: Instituto de Investigaciones Biomédicas, (CSIC-UAM), Arturo Duperier, 4, 28029, Madrid, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031, Madrid, Spain.
authors: Elena
authors: E
authors: Hernandez-Encinas
authors: Instituto de Investigaciones Biomédicas, (CSIC-UAM), Arturo Duperier, 4, 28029, Madrid, Spain.|Present Address: Departamento de Fisiología Médica y Biofísica, Instituto de Biomedicina de Sevilla, IBiS, (Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla), 41013, Sevilla, Spain.
authors: Diana
authors: D
authors: Aguilar-Morante
authors: Instituto de Investigaciones Biomédicas, (CSIC-UAM), Arturo Duperier, 4, 28029, Madrid, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031, Madrid, Spain.
authors: Jose A
authors: JA
authors: Morales-Garcia
authors: Departamento de Biología Celular, Facultad de Medicina, UCM, 28040, Madrid, Spain.
authors: Elena
authors: E
authors: Gine
authors: Instituto de Investigaciones Biomédicas, (CSIC-UAM), Arturo Duperier, 4, 28029, Madrid, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031, Madrid, Spain.
authors: Marina
authors: M
authors: Sanz-SanCristobal
authors: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031, Madrid, Spain. piedras3@med.ucm.es.|Departamento de Bioquímica y Biologia Molecular, Facultad de Medicina, UCM, 28040, Madrid, Spain. piedras3@med.ucm.es.
authors: Angel
authors: A
authors: Santos
authors: Instituto de Investigaciones Biomédicas, (CSIC-UAM), Arturo Duperier, 4, 28029, Madrid, Spain. aperez@iib.uam.es.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031, Madrid, Spain. aperez@iib.uam.es.
authors: Ana
authors: 0000-0002-2632-5853
authors: A
authors: Perez-Castillo
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D003176:Complement C3 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005452:Fluoresceins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D039481:CD11b Antigen; D003176:Complement C3; D018690:Excitatory Amino Acid Agonists; D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D012333:RNA, Messenger; C435731:fluoro jade; D007608:Kainic Acid
keywords: C/EBPβ; C3; Excitotoxicity; Neurodegeneration; Neuroinflammation