کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6279703 | 1615080 | 2016 | 23 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Intrathecal administration of rapamycin inhibits the phosphorylation of DRG Nav1.8 and attenuates STZ-induced painful diabetic neuropathy in rats
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کلمات کلیدی
PDNmTORERKDRGMWTSTZ4E-BPS6KNav1.8IRS-1Mechanical Withdrawal Thresholddorsal root ganglion - گانگلیون ریشه پشتیi.t. - آی تی.streptozotocin - استرپتوزوتوسینinsulin receptor substrate-1 - انسولین گیرنده زیربخش 1Intrathecal administration - تزریق داخل رحمیIntrathecal injection - تزریق داخل وریدیRapamycin - راپامایسینpainful diabetic neuropathy - نوروپاتی دیابتی دردناکmammalian target of rapamycin - هدف پستانداران رپامایسینribosomal protein S6 kinase - پروتئین ریبوزومی S6 کینازextracellular regulated protein kinases - پروتئین کیناز تنظیم شده خارج سلولیinsulin receptor - گیرنده انسولین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation and protein synthesis, and it is specifically inhibited by rapamycin. In chronic pain conditions, mTOR-mediated local protein synthesis is crucial for neuronal hyperexcitability and synaptic plasticity. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 plays a major role in action potential initiation and propagation and cellular excitability in DRG (dorsal root ganglion) neurons. In this study, we investigated if mTOR modulates the phosphorylation of Nav1.8 that is associated with neuronal hyperexcitability and behavioral hypersensitivity in STZ-induced diabetic rats. Painful diabetic neuropathy (PDN) was induced in Sprague-Dawley rats by intraperitoneal injection with streptozotocin (STZ) at 60 mg/kg. After the onset of PDN, the rats received daily intrathecal administrations of rapamycin (1 μg, 3 μg, or 10 μg/day) for 7 days; other diabetic rats received the same volumes of dimethyl sulfoxide (DMSO). Herein, we demonstrate a marked increase in protein expression of total mTOR and phospho-mTOR (p-mTOR) together with the up-regulation of phosphor-Nav1.8 (p-Nav1.8) prior to the mechanical withdrawal threshold reaching a significant reduction in dorsal root ganglions (DRGs). Furthermore, the intrathecal administration of rapamycin, inhibiting the activity of mTOR, suppressed the phosphorylation of DRG Nav1.8, reduced the TTX-R current density, heightened the voltage threshold for activation and lowered the voltage threshold for inactivation and relieved mechanical hypersensitivity in diabetic rats. An intrathecal injection (i.t.) of rapamycin inhibited the phosphorylation and enhanced the functional availability of DRG Nav1.8 attenuated STZ-induced hyperalgesia. These results suggest that rapamycin is a potential therapeutic intervention for clinical PDN.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 619, 21 April 2016, Pages 21-28
Journal: Neuroscience Letters - Volume 619, 21 April 2016, Pages 21-28
نویسندگان
Wan-you He, Bin Zhang, Qing-ming Xiong, Cheng-xiang Yang, Wei-cheng Zhao, Jian He, Jun Zhou, Han-bing Wang,