کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5814503 | 1556630 | 2014 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Necessary, but not sufficient: Insights into the mechanisms of mGluR mediated long-term depression from a rat model of early life seizures
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کلمات کلیدی
CaMKIIfEPSPFMRPmGluRAPVstriatal-enriched protein tyrosine phosphataseS6KaCSFTSCPP2Acalcium-calmodulin kinase IImTORDMSO - DMSOERK1/2 - ERK1 / 2S6 kinase - S6 کینازELS - آنهاlong-term depression - افسردگی طولانی مدتAutism - اوتیسم یا درخودماندگیDimethyl sulfoxide - دیمتیل سولفواکسیدartificial cerebral spinal fluid - مایع مغزی نخاعی مغزیMEK - مجاهدین خلقfield excitatory post-synaptic potentials - میدان های تحریک پذیر پس از سیناپسیmammalian target of rapamycin - هدف پستانداران رپامایسینfragile X mental retardation protein - پروتئین عقب ماندگی ذهنی X شکننده استprotein phosphatase 2A - پروتئین فسفاتاز 2Amitogen-activated protein kinase - پروتئین کیناز فعال با mitogenvoltage-gated calcium channels - کانال های کلسیم با ولتاژL-type voltage-gated calcium channel - کانال کلسیم با ولتاژ L نوعTuberous sclerosis complex - کمپلکس توبروس اسکلروزیسextracellular signal-regulated kinase 1/2 - کیناز 1/2 تنظیم سیگنال خارج سلولیSTEP - گامMetabotropic glutamate receptor - گیرنده گلوتامات متابوتروپیک
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Using the rat model of early life seizures (ELS), which has exaggerated mGluR mediated long-term depression of synaptic strength (mGluR-LTD) in adulthood, we probed the signaling cascades underlying mGluR-LTD induction. Several inhibitors completely blocked mGluR-LTD in control but not in ELS rats: the proteasome, the mammalian target of rapamycin (mTOR), S6 kinase (S6K), or L-type voltage-gated calcium channels (L-type VGCC). Inhibition of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) resulted in a near complete block of mGluR-LTD in control rats and a slight reduction of mGluR-LTD in ELS rats. “Autonomous” CaMKII was found to be upregulated in ELS rats, while elevated S6K activity, which is stimulated by mTOR, was described previously. Thus, modulation of each of these factors was necessary for mGluR-LTD induction in control rats, but even their combined, permanent activation in the ELS rats was not sufficient to individually support mGluR-LTD induction following ELS. This implies that while these factors may act sequentially in controls to mediate mGluR-LTD, this is no longer the case after ELS. In contrast, activated ERK was found to be significantly down-regulated in ELS rats. Inhibition of MEK/ERK activation in control rats elevated mGluR-LTD to the exaggerated levels seen in ELS rats. Together, these results elucidate both the mechanisms that persistently enhance mGluR-LTD after ELS and the mechanisms underlying normal mGluR-LTD by providing evidence for multiple, convergent pathways that mediate mGluR-LTD induction. With our prior work, this ties these signaling cascades to the ELS behavioral phenotype that includes abnormal working memory, fear conditioning and socialization.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 84, September 2014, Pages 1-12
Journal: Neuropharmacology - Volume 84, September 2014, Pages 1-12
نویسندگان
Paul B. Bernard, Anna M. Castano, K. Ulrich Bayer, Tim A. Benke,