کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4339707 | 1295764 | 2010 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Selective vulnerability of hippocampal cornu ammonis 1 pyramidal cells to excitotoxic insult is associated with the expression of polyamine-sensitive N-methyl-d-asparate-type glutamate receptors
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کلمات کلیدی
PNDNeuNNMDAN-methyl-d-aspartateAMPARAPVMAP-2mGluRTRITCneuron specific nuclear proteinfluorescein isothiocynateFITCPBSCREBα-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptorBDNF - BDNF یا فاکتور نورونزایی مشتقشده از مغز Ca2+ - Ca2 +Mg2+ - Mg2 +Na+ - Na +head injury - آسیب به سرamino acid - آمینو اسیدSpermidine - اسپرمیدینDL-2-Amino-5-phosphonopentanoic acid - اسید DL-2-آمینو-5-فسفونوپنتانوئیکanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceminimum essential medium - حداقل حداقل مورد نیازDIV - دیوdays in vitro - روز in vitropostnatal day - روز پس از زایمانSodium - سدیم dentate gyrus - شکنج دندانه دارbrain derived neurotrophic factor - عامل مغز استخوان مغز استخوان استMEM - مامانPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریMagnesium - منیزیمcAMP response element binding protein - پروتئین اتصال دهنده عنصر پاسخ cAMPmicrotubule associated protein-2 - پروتئین مرتبط با میکروتوبول ها 2Propidium iodide - پروتئین یدیدCalcium - کلسیمglutamate - گلوتاماتMetabotropic glutamate receptor - گیرنده گلوتامات متابوتروپیک
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Excess glutamate release and stimulation of post-synaptic glutamatergic receptors have been implicated in the pathophysiology of many neurological diseases. The hippocampus, and the pyramidal cell layer of the cornu ammonus 1 (CA1) region in particular, has been noted for its selective sensitivity to excitotoxic insults. The current studies examined the role of N-methyl-d-aspartate (NMDA) receptor subunit composition and sensitivity to stimulatory effects of the polyamine spermidine, an allosteric modulator of NMDA NR2 subunit activity, in hippocampal CA1 region sensitivity to excitotoxic insult. Organotypic hippocampal slice cultures of 8 day-old neonatal rat were obtained and maintained in vitro for 5 days. At this time, immunohistochemical analysis of mature neuron density (NeuN); microtubule associated protein-2(a,b) density (MAP-2); and NMDA receptor NR1 and NR2B subunit density in the primary cell layers of the dentate gyrus (DG), CA3, and CA1 regions, was conducted. Further, autoradiographic analysis of NMDA receptor distribution and density (i.e. [125I]MK-801 binding) and spermidine (100 μM)-potentiated [125I]MK-801 binding in the primary cell layers of these regions was examined. A final series of studies examined effects of prolonged exposure to NMDA (0.1-10 μM) on neurodegeneration in the primary cell layers of the DG, CA3, and CA1 regions, in the absence and presence of spermidine (100 μM) or ifenprodil (100 μM), an allosteric inhibitor of NR2B polypeptide subunit activity. The pyramidal cell layer of the CA1 region demonstrated significantly greater density of mature neurons, MAP-2, NR1 and NR2B subunits, and [125I]MK-801 binding than the CA3 region or DG. Twenty-four hour NMDA (10 μM) exposure produced marked neurodegeneration (â¼350% of control cultures) in the CA1 pyramidal cell region that was significantly reduced by co-exposure to ifenprodil or dl-2-Amino-5-phosphonopentanoic acid (APV). The addition of spermidine significantly potentiated [125I]MK-801 binding and neurodegeneration induced by exposure to a non-toxic concentration of NMDA, exclusively in the CA1 region. This neurodegeneration was markedly reduced with co-exposure to ifenprodil. These data suggest that selective sensitivity of the CA1 region to excitotoxic stimuli may be attributable to the density of mature neurons expressing polyamine-sensitive NR2B polypeptide subunits.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 165, Issue 2, 20 January 2010, Pages 525-534
Journal: Neuroscience - Volume 165, Issue 2, 20 January 2010, Pages 525-534
نویسندگان
T.R. Butler, R.L. Self, K.J. Smith, L.J. Sharrett-Field, J.N. Berry, J.M. Littleton, J.R. Pauly, P.J. Mulholland, M.A. Prendergast,