title: RhoGDI2 expression in astrocytes after an excitotoxic lesion in the mouse hippocampus.
abstract: The Rho GDP-dissociation inhibitor (RhoGDI) originally downregulates Rho family GTPases by preventing nucleotide exchange and membrane association. Although RhoGDI2 functions as a metastasis regulator, little is known in glial cells under neuropathological conditions. We monitored RhoGDI2 expression in the mouse brain after administering a kainic acid(KA)-induced excitotoxic lesion. In control, RhoGDI2 immunoreactivity (IR) was evident in the neuronal layer of the hippocampus. However, RhoGDI2 IR was increased in astrocytes markedly throughout the hippocampus at day 3 post-treatment with KA. To further investigate the molecular mechanism of RhoGDI2-induced cellular migration, primary astrocytes were transfected with the flag-tagged RhoGDI2 cDNA. Cell migration assay revealed that RhoGDI2 cDNA transfection inhibits astrocyte migration. Overexpression of RhoGDI2 leads to inhibit protein kinase B (PKB) activation and cdc42 and cAMP-responsive element-binding protein (CREB) phosphorylation. In conclusion, our results suggested for the first time that RhoGDI2 is required for PKB and CREB activation and cdc42 expression in astrocyte migration after KA-mediated excitotoxic lesion in mouse brain.
authors.affiliation: Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, 301-747, South Korea.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Yi
authors.forename: Kisang
authors.initials: K
authors.lastname: Kwon
authors.forename: Enji
authors.initials: E
authors.lastname: Zhang
authors.forename: Je Hoon
authors.initials: JH
authors.lastname: Seo
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
authors.forename: Chang-Gue
authors.initials: CG
authors.lastname: Son
authors.forename: Joon Won
authors.initials: JW
authors.lastname: Kang
authors.forename: Dong Woon
authors.initials: DW
authors.lastname: Kim
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D007371:Interferon-gamma / Q000494:pharmacology; D007608:Kainic Acid; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008813:Mice, Inbred ICR; D009498:Neurotoxins / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D008070:Lipopolysaccharides; D009498:Neurotoxins; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D007371:Interferon-gamma; D051057:Proto-Oncogene Proteins c-akt; D020764:cdc42 GTP-Binding Protein; D007608:Kainic Acid