کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6263041 1613828 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research ReportExcitotoxicity induced by kainic acid provokes glycogen synthase kinase-3 truncation in the hippocampus
ترجمه فارسی عنوان
گزارش تحقیقات سمیت سوشیتیک ناشی از اسید کاسیون باعث کاهش تخریب گلیکوژن سنتاز کیناز 3 در هیپوکامپ
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
چکیده انگلیسی


- GSK3 levels are decreased in CA1 hippocampal area in KA-intraperitoneal injected rats.
- GSK3 levels are decreased in CA3 hippocampal area in intra-amygdala KA microinjected mice.
- Calpain inhibition in organotypic hippocampal slices and in cultured primary neurons inhibits KA-induced GSK3 truncation.
- GSK3 truncation takes place in neurodegenerative processes in which excitotoxicity is involved.

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, our data reinforces the important relationship between glutamate receptors and GSK3 and their role in neurodegenerative processes in which excitotoxicity is involved.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1611, 22 June 2015, Pages 84-92
نویسندگان
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