کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4340953 1295817 2007 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Activity-dependent release of transforming growth factor-beta in a neuronal network in vitro
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Activity-dependent release of transforming growth factor-beta in a neuronal network in vitro
چکیده انگلیسی

For neurotrophins and also for members of the transforming growth factor beta (TGF-β) family an activity-dependent regulation of synthesis and release has been proposed. Together with the observation that the secretion of neurotransmitters is initiated by neurotrophic factors, it is reasonable to assume that they might act as retrograde modulators enhancing the efficacy and stabilization of synapses. In the present study, we have tested this hypothesis and studied the release and regulation of TGF-β in vitro using mouse primary hippocampal neurons at embryonic day E16.5 as model.We show that neuronal activity regulates TGF-β release and TGF-β expression in vitro. Treatment of the cultures with KCl, 3-veratroylveracevine (veratridine), glutamate or carbamylcholine chloride (carbachol) increased the levels of secreted TGF-β, as assessed by the MLEC/plasminogen activator inhibitor (PAI)–luciferase-assay, whereas TGF-β release stimulated by KCl or veratridine was reduced in the presence of tetrodotoxin or 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). In addition, application of glutamate significantly upregulated expression of TGF-β2 and TGF-β3 in the culture. Notably, KCl stimulation caused Smad (composite term from SMA (C. elegans) and MAD=mothers against dpp (Drosophila)) translocation into the nucleus and upregulated TGF-β inducible early gene (Tieg1) expression, demonstrating that activity-dependent released TGF-β may exert autocrine actions and thereby activate the TGF-β-dependent signaling pathway. Together, these results suggest an activity-dependent release and gene transcription of TGF-β from mouse hippocampal neurons in vitro as well as subsequent autocrine functions of the released TGF-β within the hippocampal network.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 150, Issue 3, 12 December 2007, Pages 647–657
نویسندگان
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