title: Age-dependent response of CCAAT/enhancer binding proteins following traumatic brain injury in mice.
abstract: Exacerbated inflammatory responses have been reported following traumatic injury to the aged brain. The present study was designed to investigate the involvement of the transcription factors belonging to the CCAAT/enhancer binding protein (C/EBP) family that regulate expression of many of the pro-inflammatory genes which show increased expression following injury to the aged brain. Controlled cortical impact injury was induced in adult (5-6 months) and aged (22-24 months) C57/BL6 mice. C/EBP mRNA and protein expression were analyzed in injured cortex at 1, 3, and 7 days post-injury. Expression of C/EBPalpha was reduced relative to baseline at day 1 in both adult and aged mice, whereas, it increased at days 3 and 7 post-injury. No significant differences were observed between adult and aged brain. Upregulation of C/EBPbeta was observed 1 day following injury in both the adult and aged brain, but there were no major age-related differences in mRNA levels. However, there was higher C/EBPbeta protein in the aged brain. C/EBPdelta expression increased beginning 1 day post-injury in both adult and aged brain. In this case, the increase in C/EBPdelta expression was higher in the aged brain than in the adult at all time points studied. Expression of CCAAT/enhancer binding protein homologous protein (CHOP), a transcription factor involved in ER stress and protein unfolding responses, was also up-regulated in response to injury, but CHOP levels were significantly lower in the aged than the adult brain. Based on these results, we conclude that differential expression of C/EBP beta, delta and CHOP might contribute to the hyper-inflammatory response and poor prognosis following traumatic brain injury in the elderly patients. In addition elevated C/EBPdelta levels following TBI in the aged brain may play a role in the link between TBI and Alzheimer's disease.
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
authors.forename: Nancy E J
authors.initials: NE
authors.lastname: Berman
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism / Q000503:physiopathology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017510:Protein Folding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C545013:Cebpb protein, mouse; C497253:Cebpd protein, mouse; C497250:Ddit3 protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D051743:CCAAT-Enhancer-Binding Protein-delta; D051742:Transcription Factor CHOP