Excitotoxicity induced by kainic acid provokes glycogen synthase kinase-3 truncation in the hippocampus

Brain Research
Jerónimo Jurado-ArjonaFélix Hernández

Abstract

In neuronal cultures, glycogen synthase kinase 3(GSK3) is truncated at the N-terminal end by calpain downstream of activated glutamate receptors. However, the in vivo biological significance of that truncation has not been explored. In an attempt to elucidate if GSK3 truncation has a pathophysiological relevance, we have used intraperitoneal injections of kainic acid (KA) in rats and intra-amygdala KA microinjections in mice as in vivo models of excitotoxicity. Spectrin cleavage analyzed by immunohistochemistry was observed in the CA1 hippocampal field in KA-intraperitoneal treated rats while the CA3 region was the hippocampal area affected after intra-amygdala KA microinjections. GSK3β immunofluorescence did not colocalize with truncated spectrin in both treatments using an antibody that recognize the N-terminal end of GSK3β. Thus, those neurons which are spectrin-positive do not show GSK3β immunolabelling. To study GSK3β truncation in vitro, we exposed organotypic hippocampal slices and cultured cortical neurons to KA leading to the truncation of GSK3 and we found that truncation was blocked by the calpain inhibitor calpeptin. These data suggest a relationship between N-terminal GSK3β truncation and excitotoxicity. Overall, o...Continue Reading

References

Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·R BeyaertW Fiers
Apr 5, 2000·The Journal of Biological Chemistry·G KusakawaS Hisanaga
Aug 23, 2001·Trends in Molecular Medicine·Y Huang, K K Wang
Jul 5, 2003·Physiological Reviews·Darrell E GollJinyang Cong
Apr 23, 2004·Trends in Biochemical Sciences·Richard S Jope, Gail V W Johnson
Jul 2, 2005·Cellular and Molecular Life Sciences : CMLS·A Czogalla, A F Sikorski
Sep 9, 2006·CNS Drug Reviews·Antoni CaminsMercè Pallàs
Mar 3, 2007·Neuron·Stéphane PeineauGraham L Collingridge
Jun 16, 2007·The Journal of Biological Chemistry·Paloma Goñi-OliverFélix Hernández
Sep 23, 2009·Apoptosis : an International Journal on Programmed Cell Death·Zhiqun ZhangKevin K W Wang
Jul 20, 2010·Bipolar Disorders·Natalia Crespo-BielMercè Pallàs

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Citations

Mar 7, 2017·PloS One·Anna P MillerAleksandra Glavaski-Joksimovic
Jan 15, 2016·Journal of Lipid Research·Miguel A Martín-AcebesJuan-Carlos Saiz

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