کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6017374 | 1580160 | 2015 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
LY395756, an mGluR2 agonist and mGluR3 antagonist, enhances NMDA receptor expression and function in the normal adult rat prefrontal cortex, but fails to improve working memory and reverse MK801-induced working memory impairment
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کلمات کلیدی
ACPDcyclic-adenosine monophosphateVAMPmGluRsGSK3βNMDARPKCDCG-IVi.p.SNAREAMPAAMPHpKaAPDC3,5-dihydroxyphenylglycine - 3،5-دی هیدروکسی فنیل گلیسینcAMP - cAMPERK1/2 - ERK1 / 2extracellular signal-regulated kinase1/2 - kinase1 / 2 تنظیم شده سیگنال خارج سلولیNMDA receptor - NMDA گیرندهSCZ - SBSadenylate cyclase - آدنیلات سیکلاسAmphetamine - آمفتامین هاSchizophrenia - اسکیزوفرنی یا شیزوفرنیα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid - اسید α-آمینو 3-هیدروکسی-5-متیل-4-ایزوکسول پپونیکintraperitoneal - داخل صفاقیdihydroxyphenylglycine - دی هیدروکسی فنیل گلیسینProtein synthesis - سنتز پروتئینmTOR signaling - سیگنالینگ mTORSNAP - ضربه محکم و ناگهانیCognitive function - عملکرد شناختیprefrontal cortex - قشر prefrontalAnimal model - مدل حیوانیVesicle-associated membrane protein - پروتئین غشاء مرتبط با Vesicleprotein kinase A - پروتئین کیناز AProtein kinase C - پروتئین کیناز سیSingle nucleotide polymorphism - پلیمورفیسم تک نوکلئوتیدیSNP - چندریختی تک-نوکلئوتیدGABA - گاباGlycogen synthase kinase 3β - گلیکوزین سنتاز کیناز 3βN-methyl-d-aspartate receptor - گیرنده N-methyl-d-aspartateMetabotropic glutamate receptors - گیرنده های متابوتروپیک گلوتامات
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Targeting group II metabotropic glutamate receptors (mGluR2/3) has been proposed to correct the dysfunctional glutamatergic system, particularly NMDA receptor (NMDAR) hypofunction, for treatment of schizophrenia. However, how activation of mGluR2/3 affects NMDAR function in adult animals remains elusive. Here we show the effects of LY395756 (LY39), a compound acting as both an mGluR2 agonist and mGluR3 antagonist, on the NMDAR expression and function of normal adult rat prefrontal cortex (PFC) as well as working memory function in the MK801 model of schizophrenia. We found that in vivo administration of LY39 significantly increased the total protein levels of NMDAR subunits and NR2B phosphorylationin the PFC, along with the amplitude of NMDAR-mediated miniature excitatory postsynaptic currents (mEPSC) in the prefrontal cortical neurons. Moreover, LY39 also significantly increased mTOR and pmTOR expression, but not ERK1/2, Akt, and GSK3β, suggesting an activation of mTOR signaling. Indeed, the mTOR inhibitor rapamycin, and actinomycin-D, a transcription inhibitor, blocked the enhanced effects of LY39 on NMDAR-mEPSCs. These results indicate that LY39 regulates NMDAR expression and function through unidentified mTOR-mediated protein synthesis in the normal adult rat PFC. However, this change is insufficient to affect working memory function in normal animals, nor to reverse the MK801-induced working memory deficit. Our data provide the first evidence of an in vivo effect of a novel compound that acts as both an mGluR2 agonist and mGluR3 antagonist on synaptic NMDAR expression and function in the adult rat PFC, although its effect -on PFC-dependent cognitive function remains to be explored.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 273, November 2015, Pages 190-201
Journal: Experimental Neurology - Volume 273, November 2015, Pages 190-201
نویسندگان
Meng-Lin Li, Sha-Sha Yang, Bo Xing, Brielle R. Ferguson, Yelena Gulchina, Yan-Chun Li, Feng Li, Xi-Quan Hu, Wen-Jun Gao,