کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4343313 1615091 2015 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Down-regulation of astroglial glutamate transporter-1 in the locus coeruleus impairs pain-evoked endogenous analgesia in rats
ترجمه فارسی عنوان
تنظیم مقادیر حملونقل 1-گلوتامات آسترگلیال در لوسوس کوئرولوس باعث کاهش درد ناشی از درد ناشی از درد در موش صحرایی می شود
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
چکیده انگلیسی


• Down-regulating GLT-1 increases basal extracellular glutamate level in the LC.
• Elevated basal glutamate reduces pain-evoked glutamate release in the LC.
• Elevated basal glutamate increases basal but reduces pain-evoked LC activity.
• Glutamate dysregulation in the LC impairs pain-evoked endogenous analgesia.

Descending noradrenergic inhibition to the spinal cord from the locus coeruleus (LC) is an important endogenous pain-relief mechanism which can be activated by local glutamate signaling. Here we tested whether dysregulation of extracellular glutamate level in the LC induced by down-regulating astroglial glutamate transporter-1(GLT-1) impairs endogenous analgesia. In rats treated with repeated LC injections of GLT-1 selective or non-targeting small interfering RNA (siRNA), a subdermal injection of capsaicin was used to examine noxious stimulation-induced analgesia (NSIA), evoked LC glutamate and spinal noradrenaline release, and evoked LC neuronal activity. LC-injected GLT-1 siRNA reduced expression of GLT-1 in the LC (P = 0.02), increased basal activity of LC neurons (P < 0.01), and increased basal extracellular concentrations of LC glutamate (P < 0.01) and spinal noradrenaline (P < 0.01), but did not affect mechanical withdrawal thresholds in the hindpaw (P = 0.83), compared to non-targeting siRNA. LC-injected GLT-1 siRNA impaired capsaicin-evoked release of LC glutamate and spinal noradrenaline, capsaicin-evoked LC neuronal activation, and NSIA. These results suggest that astroglial GLT-1 is essential to normal LC function and that increased extracellular glutamate by down-regulating GLT-1 impairs evoked LC activity and NSIA, essentially taking the LC “off-line”.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 608, 3 November 2015, Pages 18–22
نویسندگان
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