کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4351590 1615307 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Glutamate attenuates IGF-1 receptor tyrosine phosphorylation in mouse brain: Possible significance in ischemic brain damage
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Glutamate attenuates IGF-1 receptor tyrosine phosphorylation in mouse brain: Possible significance in ischemic brain damage
چکیده انگلیسی

We have previously reported that glutamate acting on NMDA receptors attenuated IGF-1 pro-survival signaling and its protective effect in cultured neurons. In this study, we investigate whether IGF-1 signaling was suppressed by glutamate in vivo, and whether this effect of glutamate was implicated in ischemic brain damage. Our results showed that exogenous glutamate injected by i.c.v. decreased phosphorylation of IGF-1 receptors and Akt, and this effect of glutamate was reversed by NMDA antagonist MK-801 but not by non-NMDA antagonist DNQX. NMDA exhibited similar effects of glutamate. Endogenous glutamate, which was induced by focal cerebral ischemia, gradually reduced the phosphorylation of IGF-1 receptors and Akt in a time-dependent manner. Moreover, IGF-1 injected by i.c.v. failed to stimulate phosphorylation of IGF-1 receptors and Akt after 180 min MCAO, and the protective effect was abolished. Pre-treatment of MK-801 restored the phosphorylation of IGF-1 receptors and Akt by IGF-1. In parallel, IGF-1 successfully rescued infarct area after 180 min MCAO. These findings suggest that glutamate interferes with IGF-1 signaling in vivo by activating NMDA receptors, and thereby shorten the therapeutic window of IGF-1 against focal cerebral ischemia.


► IGF-1 signaling is attenuated by glutamate in vivo by i.c.v. injection.
► NMDA exhibits similar effect of glutamate.
► Excessive glutamate release during stroke attenuates IGF-1 signaling in the receptor level.
► MK801 abolishes the inhibitory effect of glutamate and prolongs the therapeutic window of IGF-1.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Research - Volume 74, Issues 3–4, December 2012, Pages 290–297
نویسندگان
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