Remodeling of striatal NMDA receptors by chronic A2A receptor blockade in Huntington's disease mice

Abstract Excitotoxicity plays a major role in the pathogenesis of Huntington disease (HD), a fatal neurodegenerative disorder. Adenosine A2A receptors (A2A 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...

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Published in:Neurobiology of disease 2010-01, Vol.37 (1), p.99-105
Main Authors: Martire, Alberto, Ferrante, Antonella, Potenza, Rosa Luisa, Armida, Monica, Ferretti, Roberta, Pézzola, Antonella, Domenici, Maria Rosaria, Popoli, Patrizia
Format: Article
Language:English
Subjects:
Adenosine A2A receptor
BDNF
Huntington disease
Neurology
NMDA receptor subunit
R6/2 mice
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Summary:Abstract Excitotoxicity plays a major role in the pathogenesis of Huntington disease (HD), a fatal neurodegenerative disorder. Adenosine A2A receptors (A2A 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 A2A 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 A2A 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 A2A Rs in HD.
ISSN:0969-9961
1095-953X
DOI:10.1016/j.nbd.2009.09.012