کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5813302 | 1556612 | 2016 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Persistent elevation of D-Aspartate enhances NMDA receptor-mediated responses in mouse substantia nigra pars compacta dopamine neurons
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کلمات کلیدی
d-aspmedial terminal nucleusL-Aspartateβ-N-methylamino-l-alanineDAergicL-ASPdDOEAATsaCSFBMAASNCd-aspartate - D-آسپارتاتd-aspartate oxidase - D-آسپارتات اکسیدازNMDA receptor - NMDA گیرندهsubstantia nigra pars compacta - توده سیاه پارس متراکمexcitatory amino-acid transporter - حمل و نقل آمینو اسید هیجان انگیزcell capacitance - خازن سلولیDopamine - دوپامینDopaminergic - دوپامینرژیکartificial cerebrospinal fluid - مایع مغزی نخاعی مصنوعیMembrane resistance - مقاومت غشاء
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Persistent elevation of D-Aspartate enhances NMDA receptor-mediated responses in mouse substantia nigra pars compacta dopamine neurons Persistent elevation of D-Aspartate enhances NMDA receptor-mediated responses in mouse substantia nigra pars compacta dopamine neurons](/preview/png/5813302.png)
چکیده انگلیسی
Dopamine neurons in the substantia nigra pars compacta regulate not only motor but also cognitive functions. NMDA receptors play a crucial role in modulating the activity of these cells. Considering that the amino-acid D-Aspartate has been recently shown to be an endogenous NMDA receptor agonist, the aim of the present study was to examine the effects of D-Aspartate on the functional properties of nigral dopamine neurons. We compared the electrophysiological actions of D-Aspartate in control and D-aspartate oxidase gene (Ddoâ/â) knock-out mice that show a concomitant increase in brain D-Aspartate levels, improved synaptic plasticity and cognition. Finally, we analyzed the effects of L-Aspartate, a known dopamine neuron endogenous agonist in control and Ddoâ/â mice. We show that D- and L-Aspartate excite dopamine neurons by activating NMDA, AMPA and metabotropic glutamate receptors. Ddo deletion did not alter the intrinsic properties or dopamine sensitivity of dopamine neurons. However, NMDA-induced currents were enhanced and membrane levels of the NMDA receptor GluN1 and GluN2A subunits were increased. Inhibition of excitatory amino-acid transporters caused a marked potentiation of D-Aspartate, but not L-Aspartate currents, in Ddoâ/â neurons. This is the first study to show the actions of D-Aspartate on midbrain dopamine neurons, activating not only NMDA but also non-NMDA receptors. Our data suggest that dopamine neurons, under conditions of high D-Aspartate levels, build a protective uptake mechanism to compensate for increased NMDA receptor numbers and cell hyper-excitation, which could prevent the consequent hyper-dopaminergia in target zones that can lead to neuronal degeneration, motor and cognitive alterations.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 103, April 2016, Pages 69-78
Journal: Neuropharmacology - Volume 103, April 2016, Pages 69-78
نویسندگان
Paraskevi Krashia, Ada Ledonne, Annalisa Nobili, Alberto Cordella, Francesco Errico, Alessandro Usiello, Marcello D'Amelio, Nicola Biagio Mercuri, Ezia Guatteo, Irene Carunchio,