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.
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This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2013R1A1A1A05006966) and by Chungnam National University Hospital Research Fund, 2013.
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The authors declare no financial or other conflicts of interest related to this study.
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Min-Hee Yi and Kisang Kwon have contributed equally to this work.
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Yi, MH., Kwon, K., Zhang, E. et al. RhoGDI2 Expression in Astrocytes After an Excitotoxic Lesion in the Mouse Hippocampus. Cell Mol Neurobiol 35, 167–174 (2015). https://doi.org/10.1007/s10571-014-0108-z
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DOI: https://doi.org/10.1007/s10571-014-0108-z