Adenosine A2A receptor antagonists exert motor and neuroprotective effects by distinct cellular mechanisms.
Ann Neurol
; 63(3): 338-46, 2008 Mar.
Article
en En
| MEDLINE
| ID: mdl-18300283
ABSTRACT
OBJECTIVE:
To investigate whether the motor and neuroprotective effects of adenosine A(2A) receptor (A(2A)R) antagonists are mediated by distinct cell types in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease.METHODS:
We used the forebrain A(2A)R knock-out mice coupled with flow cytometric analyses and intracerebroventricular injection to determine the contribution of A(2A)Rs in forebrain neurons and glial cells to A(2A)R antagonist-mediated motor and neuroprotective effects.RESULTS:
The selective deletion of A(2A)Rs in forebrain neurons abolished the motor stimulant effects of the A(2A)R antagonist KW-6002 but did not affect acute MPTP neurotoxicity. Intracerebroventricular administration of KW-6002 into forebrain A(2A)R knock-out mice reinstated protection against acute MPTP-induced dopaminergic neurotoxicity and attenuated MPTP-induced striatal microglial and astroglial activation.INTERPRETATION:
A(2A)R activity in forebrain neurons is critical to the control of motor activity, whereas brain cells other than forebrain neurons (likely glial cells) are important components for protection against acute MPTP toxicity.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fármacos Neuroprotectores
/
Antagonistas del Receptor de Adenosina A2
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Actividad Motora
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Ann Neurol
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos