کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4323769 1613812 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Exendin-4 antagonizes Aβ1-42-induced suppression of long-term potentiation by regulating intracellular calcium homeostasis in rat hippocampal neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Exendin-4 antagonizes Aβ1-42-induced suppression of long-term potentiation by regulating intracellular calcium homeostasis in rat hippocampal neurons
چکیده انگلیسی


• Exendin-4 suppressed Aβ-induced [Ca2+]i elevation through L-VDCC and NMDA receptor.
• Exendin-4 antagonized decline of p-CaMKIIα induced by Aβ1-42.
• Exendin-4 is likely to regulate calcium homeostasis to perform neuroprotection.
• The study provides a support for Exendin-4 being used to treat and prevent AD.
• The LTP was investigated with homemade stimulation/recording/drug delivery system.

An imbalance of intracellular calcium homeostasis induced by amyloid β-protein (Aβ) contributes to the pathogenesis of Alzheimer׳s disease (AD), such as deficits in learning and memory. Therefore, regulation of calcium homeostasis may represent a new strategy for treatment of AD. Growing evidence suggests that type 2 diabetes mellitus (T2DM) and AD are closely related in pathogenesis. Thus, drugs used in treatment of T2DM may modify the pathogenesis of AD. This study demonstrated that Exendin-4, which is a glucagon-like peptide-1 (GLP-1) analog used as a therapeutic drug for T2DM, significantly antagonized suppression of long-term potentiation (LTP) induced by Aβ1-42 in the rat hippocampal CA1 region in vivo. This neuroprotection may be mediated by regulation of calcium homeostasis. Pretreatment with Exendin-4 suppressed Aβ1-42-induced elevation in intracellular calcium concentration ([Ca2+]i) through L-type voltage-dependent calcium channels (L-VDCCs) and N-methyl-D-aspartate receptors (NMDARs). Furthermore, Exendin-4 antagonized the decrease in p-Ca2+/calmodulin-dependent protein kinase IIα (p-CaMKIIα) induced by Aβ1-42 in the rat hippocampal CA1 region. Thus, the neuroprotective effects of Exendin-4, which likely involve regulation of calcium homeostasis, provide theoretical support for using Exendin-4 to treat and prevent AD in the future.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1627, 19 November 2015, Pages 101–108
نویسندگان
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