Abstract
Repeated seizures induce permanent alterations in the hippocampal circuits in experimental models with intractable temporal lobe epilepsy. Sprouting and synaptic reorganization induced by seizures has been well-studied in the mossy fiber pathway. However, studies investigating sprouting and synaptic reorganization beyond the mossy fiber pathway are limited. The present study examined the biochemical changes of CA1 pyramidal neurons undergoing morphological changes after excitotoxicity-induced hippocampal CA3 neuronal death. IQ-domain GTPase-activating proteins (IQGAP1), is an effector of Rac1 and Cdc42 and an actin-binding protein, was upregulated in CA1 pyramidal neurons after kainic acid-induced hippocampal CA3 neuronal degeneration. IQGAP1 + cells were colocalized with Nestin, but not in astrocytes or mature neurons. Furthermore, IQGAP1 did not originate from newly divided local precursors or NG2 + cells. IQGAP1 and adenomatous polyposis coli localized in CA1 pyramidal neurons, and Cdc42 activation was followed by IQGAP1 recruitment. These findings suggest that IQGAP1 is upregulated in pre-existed sparing neurons of the CA1 layer undergoing morphological changes after excitoxicity-induced hippocampal CA3 neuronal death. It demonstrates the utility of IQGAP1 as a possible marker for spared pyramidal neurons, which may contribute to structural and functional alternations responsible for the development of epilepsy.
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Acknowledgments
We thank Tae Kewn Lim for valuable assistance with our immunohistochemical analysis. This study was financially supported by research fund of Chungnam National University in 2011.
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Min-Hee Yi and Sooil Kim contributed equally to this study.
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Yi, MH., Kim, S., Zhang, E. et al. IQGAP1 Expression in Spared CA1 Neurons After an Excitotoxic Lesion in the Mouse Hippocampus. Cell Mol Neurobiol 33, 1003–1012 (2013). https://doi.org/10.1007/s10571-013-9968-x
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DOI: https://doi.org/10.1007/s10571-013-9968-x