کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6278232 | 1295800 | 2009 | 20 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Altered mnemonic functions and resistance to N-METHYL-d-Aspartate receptor antagonism by forebrain conditional knockout of glycine transporter 1
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کلمات کلیدی
Cre-recombinaseevoked excitatory postsynaptic currenteEPSCNBQXTBSTCaMKIIαNMDARGlyT12,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dionePGKITITRISaCSFAMPARTriton-X 100ANCOVAPCPHEPESTween 20Emx1Strychnine-sensitive glycine receptor4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid - 4- (2-hydroxyethyl) -1-piperazineethanesulfonic acidEPSC - EPSCoRNPE - NAMENMDA receptor - NMDA گیرندهtris-(hydroxymethyl)-aminomethane - tris- (hydroxymethyl) -aminomethaneEDTA - اتیلن دی آمین تترا استیک اسید Schizophrenia - اسکیزوفرنی یا شیزوفرنیSDS-PAGE - الکتروفورز ژل پلی آکریل آمیدsodium dodecylsulfate polyacrylamide gel electrophoresis - الکتروفورز ژل پلی اکریللید سدیم دودسیل سولفاتanalysis of covariance - تجزیه و تحلیل کوواریانسanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceexcitatory postsynaptic current - جریان پستیینپتیک تحریک کنندهPsychopharmacology - روان داروشناسی، سایکوفارماکولوژیintertrial interval - فاصله بین فضاییphosphoglycerate kinase - فسفوگلیسرات کینازPhencyclidine - فن سیکلیدین، گرد فرشتهartificial cerebrospinal fluid - مایع مغزی نخاعی مصنوعیconditioned stimulus - محرک شرطیLatent inhibition - مهار خاموشpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازAMPA receptor - گیرنده AMPAN-methyl-d-aspartate receptor - گیرنده N-methyl-d-aspartateglycine transporter 1 - گیرنده گلیسین 1Learning - یادگیری
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Converging evidence from pharmacological and molecular studies has led to the suggestion that inhibition of glycine transporter 1 (GlyT1) constitutes an effective means to boost N-methyl-d-aspartate receptor (NMDAR) activity by increasing the extra-cellular concentration of glycine in the vicinity of glutamatergic synapses. However, the precise extent and limitation of this approach to alter cognitive function, and therefore its potential as a treatment strategy against psychiatric conditions marked by cognitive impairments, remain to be fully examined. Here, we generated mutant mice lacking GlyT1 in the entire forebrain including neurons and glia. This conditional knockout system allows a more precise examination of GlyT1 downregulation in the brain on behavior and cognition. The mutation was highly effective in attenuating the motor-stimulating effect of acute NMDAR blockade by phencyclidine, although no appreciable elevation in NMDAR-mediated excitatory postsynaptic currents (EPSC) was observed in the hippocampus. Enhanced cognitive performance was observed in spatial working memory and object recognition memory while spatial reference memory and associative learning remained unaltered. These findings provide further credence for the potential cognitive enhancing effects of brain GlyT1 inhibition. At the same time, they indicated potential phenotypic differences when compared with other constitutive and conditional GlyT1 knockout lines, and highlighted the possibility of a functional divergence between the neuronal and glia subpopulations of GlyT1 in the regulation of learning and memory processes. The relevance of this distinction to the design of future GlyT1 blockers as therapeutic tools in the treatment of cognitive disorders remains to be further investigated.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 161, Issue 2, 30 June 2009, Pages 635-654
Journal: Neuroscience - Volume 161, Issue 2, 30 June 2009, Pages 635-654
نویسندگان
P. Singer, B.K. Yee, J. Feldon, T. Iwasato, S. Itohara, T. Grampp, G. Prenosil, D. Benke, H. Möhler, D. Boison,