کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8841165 | 1614707 | 2018 | 41 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The Hypoxia Mimetic Protocatechuic Acid Ethyl Ester Inhibits Synaptic Signaling and Plasticity in the Rat Hippocampus
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کلمات کلیدی
PHDHFSNMDARAP-5PPRHIFHREaCSFAMPARDesferrioxamineDMOGMDGDFOCA1dimethyloxaloylglycine(2R)-amino-5-phosphonovaleric acid - (2R) آمینو 5-فسفونوالریک اسید2-OG - 2 و2-oxoglutarate - 2-اگزوگلوتراتDMSO - DMSOEPSP - epspifEPSPs - fEPSP هاα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor - α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptorcornu Ammonis 1 - آمون شاخ 1high-frequency stimulation - تحریک فرکانس بالاlong-term potentiation - تقویت درازمدتLTP - تقویت طولانی مدت یا LTP DIV - دیوDimethyl sulfoxide - دیمتیل سولفواکسیدdays in vitro - روز in vitrohypoxia-responsive element - عنصر حساس به هیپوکسیHypoxia-inducible factor - فاکتور القاء کننده هیپوکسیartificial cerebrospinal fluid - مایع مغزی نخاعی مصنوعیpaired pulse ratio - نسبت پالس زوجیHippocampus - هیپوکامپ Hypoxia - هیپوکسیfield excitatory postsynaptic potentials - پتانسیل پستنیپتیک تحریک پذیری میدانPropidium iodide - پروتئین یدیدProlyl hydroxylase - پرولیل هیدروکسیلازGABAR - گابارN-methyl-d-aspartate receptor - گیرنده N-methyl-d-aspartateγ-aminobutyric acid receptor - گیرنده اسید γ-آمینوآبتیریک
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
During hypoxia a number of physiological changes occur within neurons including the stabilization of hypoxia-inducible factors (HIFs). The activity of these proteins is regulated by O2, Fe2+, 2-OG and ascorbate-dependant hydroxylases which contain prolyl-4-hydroxylase domains (PHDs). PHD inhibitors have been widely used and have been shown to have a preconditioning and protective effect against a later and more severe hypoxic insult. In this study we have investigated the neuroprotective effects of the PHD inhibitor, protocatechuic acid ethyl ester (ethyl 3,4, dihydroxybenzoate: EDHB), as well as its effects on synaptic transmission and plasticity in the rat hippocampus using electrophysiological techniques. We report for the first time, an acute concentration-dependent and reversible inhibitory effect of EDHB (10-100â¯Î¼M) on synaptic transmission in the dentate gyrus but not Cornu Ammonis 1 (CA1) region which does not affect cell viability. This effect was attenuated through the application of the NMDA or GABAA receptor antagonists, AP-5 and picrotoxin in the dentate gyrus. There were no changes in the ratio of paired responses after EDHB application suggesting a post-synaptic mechanism of action. EDHB (100â¯Î¼M), was found to inhibit synaptic plasticity in both the dentate gyrus and CA1 regions. Application of exogenous Fe2+ (100â¯Î¼M) or digoxin (100â¯nM) did not reverse EDHB's inhibitory effect on synaptic transmission or plasticity in both regions, suggesting that its effects may be HIF-independent. These results highlight a novel modulatory role for the PHD inhibitor EDHB in hippocampal synaptic transmission and plasticity. A novel post-synaptic mechanism of action may be involved, possibly involving NMDA and GABAA receptor activation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 369, 15 January 2018, Pages 168-182
Journal: Neuroscience - Volume 369, 15 January 2018, Pages 168-182
نویسندگان
Sinead M. Lanigan, John J. O'Connor,