کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10958515 1100078 2005 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effects of positive AMPA receptor modulators on calpain-mediated spectrin degradation in cultured hippocampal slices
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Effects of positive AMPA receptor modulators on calpain-mediated spectrin degradation in cultured hippocampal slices
چکیده انگلیسی
Positive modulators of AMPA receptors (AMPAr), also known as ampakines, are allosteric effectors of the receptors and have been extensively studied in past years due to their potential use as treatment for various diseases and ailments of the central nervous system such as mild cognitive impairment, schizophrenia, and Alzheimer's disease. Ampakines have been shown to improve performance on memory tasks in animals and in human subjects, an effect linked to their ability to increase agonist-mediated ion influx through AMPAr, thus leading to enhanced synaptic responses and facilitation of long-term potentiation (LTP) induction at glutamatergic synapses. As LTP is associated with calpain activation and spectrin degradation, we determined the effects of ampakine treatment of cultured hippocampal slices on spectrin degradation. Calpain activation was evaluated by determining the levels of the 145-150 kDa degradation products of spectrin. Our data indicated that incubation of hippocampal slices with some, but not all positive modulators of AMPA receptors resulted in enhanced spectrin degradation, an effect that was blocked by a calpain inhibitor. In addition, an antagonist of AMPAr but not of NMDAr blocked ampakine-induced spectrin degradation. These results indicate that prolonged treatment with selected ampakines leads to spectrin degradation mediated by activation of the calcium-dependent protease calpain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 46, Issue 1, January 2005, Pages 31-40
نویسندگان
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