Remodeling of striatal NMDA receptors by chronic A(2A) receptor blockade in Huntington's disease mice.
Excitotoxicity plays a major role in the pathogenesis of Huntington disease (HD), a fatal neurodegenerative disorder. Adenosine A(2A) receptors (A(2A)Rs) modulate excitotoxicity and have been suggested to play a pathogenetic role in HD. The main aim of this study was to evaluate the effect of A(2A)R blockade on the expression and functions of NMDA receptors in the striatum of HD mice (R6/2). We found that 3 weeks' treatment with SCH 58261 (0.01 mg/kg/day i.p. from the 8th week of age) modified NR1 and NR2A/NR2B expression in the striatum of R6/2 (Western blotting) while had no effect on NMDA-induced toxicity in corticostriatal slices (electrophysiological experiments). In conclusion, in vivo A(2A)R blockade induced a remodeling of NMDA receptors in the striatum of HD mice. Even though the functional relevance of the above effect remains to be fully elucidated, these results add further evidence to the modulatory role of A(2A)Rs in HD.
Martire
Alberto
A
Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
Ferrante
Antonella
A
Potenza
Rosa Luisa
RL
Armida
Monica
M
Ferretti
Roberta
R
Pézzola
Antonella
A
Domenici
Maria Rosaria
MR
Popoli
Patrizia
P
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006816:Huntington Disease / Q000188:drug therapy* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000633:toxicity; D009473:Neuronal Plasticity / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity; D011743:Pyrimidines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058917:Adenosine A2 Receptor Antagonists; D019208:Brain-Derived Neurotrophic Factor; D002491:Central Nervous System Agents; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D009498:Neurotoxins; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D016194:Receptors, N-Methyl-D-Aspartate; D014230:Triazoles; D016202:N-Methylaspartate; D020813:Receptor, trkB