title: Upregulation of gp130 and STAT3 activation in the rat hippocampus following transient forebrain ischemia.
abstract: To determine whether the pathophysiological processes after transient forebrain ischemia are mediated via a signal pathway involving gp130 (a signal transducer for the interleukin-6 family), we analyzed changes in the expression of gp130 and its downstream transcription factor, signal transducer and activator of transcription factor 3 (STAT3), in the rat hippocampus of a four-vessel occlusive ischemia model. Expression of gp130 mRNA was restricted to neurons of the pyramidal cell and granule cell layers in control animals. Four hours after ischemic injury, astrocytes expressed gp130 mRNA. Expression of gp130 increased preferentially in the CA1 and dentate hilar regions, and was maintained for at least 2 weeks. Increase in gp130 expression was accompanied by the activation of STAT3 following ischemic injury. Four hours after injury, STAT3 and phosphorylated STAT3 (pSTAT3) were observed in the nuclei of the dentate hilar region, and sequentially in the CA1 region at day 1. By day 3, STAT3 immunoreactivity markedly increased in these areas, where small cells with the morphology of astrocytes showed nuclear and cytoplasmic STAT3 and nuclear pSTAT3 immunoreactivities. These patterns were especially maintained in the CA1 area until 14 days of reperfusion. Double-labeling experiments revealed that the cells expressing STAT3 and pSTAT3 were glial fibrillary acidic protein-expressing reactive astrocytes. These results show a coordinated and long-lasting upregulation of gp130 mRNA and STAT3 activation in reactive astrocytes of the postischemic hippocampus, indicating that they may be involved in the astrocytic response to an ischemic insult.
authors.affiliation: Department of Anatomy, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Choi
authors.forename: Seong Yun
authors.initials: SY
authors.lastname: Kim
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Cha
authors.forename: Yun-Sik
authors.initials: YS
authors.lastname: Choi
authors.forename: Ki-Wug
authors.initials: KW
authors.lastname: Sung
authors.forename: Seong Taek
authors.initials: ST
authors.lastname: Oh
authors.forename: Ok Nyu
authors.initials: ON
authors.lastname: Kim
authors.forename: Jin-Woong
authors.initials: JW
authors.lastname: Chung
authors.forename: Myung-Hoon
authors.initials: MH
authors.lastname: Chun
authors.forename: Sang Bok
authors.initials: SB
authors.lastname: Lee
authors.forename: Mun-Yong
authors.initials: MY
authors.lastname: Lee
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017966:Pyramidal Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor; D020521:Stroke / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494201:Il6st protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D050822:Cytokine Receptor gp130