کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5737665 1614717 2017 42 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sigma 1 receptor activation modifies intracellular calcium exchange in the G93AhSOD1 ALS model
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Sigma 1 receptor activation modifies intracellular calcium exchange in the G93AhSOD1 ALS model
چکیده انگلیسی
Here, we used cultured embryonic mice spinal neurons to investigate the influence of Sig1R activation on intracellular Ca2+ homeostasis in the presence of G93AhSOD1 (G93A), an established ALS-causing mutation. Sig1R expression was increased in G93A motor neurons relative to non-transgenic (nontg) controls. Furthermore, we demonstrated significantly reduced bradykinin-sensitive intracellular Ca2+ stores in G93A spinal neurons, which were normalized by the Sig1R agonist SA4503. Moreover, SA4503 accelerated cytosolic Ca2+ clearance following a) AMPAR activation by kainate and b) IP3R-mediated ER Ca2+ release following bradykinin stimulation in both genotypes. PRE-084 (another Sig1R agonist) did not exert any significant effects on cytosolic Ca2+. Both Sig1R expression and functionality were altered by the G93A mutation, indicating the centrality of Sig1R in ALS pathology. Here, we showed that intracellular Ca2+ shuttling can be manipulated by Sig1R activation, thus demonstrating the value of using the pharmacological manipulation of Sig1R to understand Ca2+ homeostasis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 359, 17 September 2017, Pages 105-118
نویسندگان
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