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Titolo:
Rescue of locomotor impairment in dopamine D2 receptor-deficient mice by an adenosine A2A receptor antagonist
Autore:
Aoyama, S; Kase, H; Borrelli, E;
Indirizzi:
Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch, CU Strasbourg, France Inst Genet & Biol Mol & Cellulaire Illkirch CU Strasbourg France F-67404 Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Inst, Nagaizumi, Shizuoka 4118731, Japan Kyowa Hakko Kogyo Co Ltd Nagaizumi Shizuoka Japan 4118731 4118731, Japan
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 15, volume: 20, anno: 2000,
pagine: 5848 - 5852
SICI:
0270-6474(20000801)20:15<5848:ROLIID>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENKEPHALIN-GENE-EXPRESSION; A(2A) RECEPTOR; BASAL GANGLIA; MEDIATED MODULATION; D-2 RECEPTORS; SPINY NEURONS; RAT STRIATUM; LOCALIZATION; NEOSTRIATUM; HALOPERIDOL;
Keywords:
adenosine A2 receptor; dopamine D2 receptor; striatum; KW-6002; Parkinson's disease; knockout mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Borrelli, E Inst Genet & Biol Mol & Cellulaire, BP163, F-67404 Illkirch, CU Strasbourg, France Inst Genet & Biol Mol & Cellulaire BP163 Illkirch CU Strasbourg France F-67404
Citazione:
S. Aoyama et al., "Rescue of locomotor impairment in dopamine D2 receptor-deficient mice by an adenosine A2A receptor antagonist", J NEUROSC, 20(15), 2000, pp. 5848-5852

Abstract

In Parkinson's disease a degeneration of dopaminergic neurons of the nigrostriatal pathway is observed. Loss of dopaminergic regulation of striatal neuron activity results in altered motor functions. Adenosine A2A (A2AR) anddopamine D2 (D2R) receptors are colocalized in striatal medium spiny neurons. It has been proposed that adenosine binding to A2AR lowers the affinityof dopamine for D2R, thus modulating the function of this receptor. Absence of D2R in knockout mice (D2R-/-) results in impaired locomotion and coordinated movements. This indicates that absence of dopamine in Parkinson's disease might principally affect D2R-mediated effects with regard to locomotor functions. A2AR-selective antagonists have been demonstrated to have antiparkinsonian activities in various models of Parkinson's disease in rodentsand nonhuman primates. In this article, D2R-/- mice were used to explore the possibility that an A2AR antagonist might reestablish their motor impairment. Interestingly, blockade of A2AR rescues the behavioral parameters altered in D2R-/- mice. In addition, the level of expression of enkephalin andsubstance P, which were altered in D2R-/-, were also reestablished to normal levels after A2AR antagonist treatment. These results show that A2AR andD2R have antagonistic and independent activities in controlling neuronal and motor functions in the basal ganglia. They also provide evidence that selective A2AR antagonists can exhibit their anti-parkinsonian activities through a nondopaminergic mechanism.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 18:30:02