Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors.
Mol Psychiatry
; 25(8): 1876-1900, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-29950682
ABSTRACT
Synaptic dysfunction plays a central role in Alzheimer's disease (AD), since it drives the cognitive decline. An association between a polymorphism of the adenosine A2A receptor (A2AR) encoding gene-ADORA2A, and hippocampal volume in AD patients was recently described. In this study, we explore the synaptic function of A2AR in age-related conditions. We report, for the first time, a significant overexpression of A2AR in hippocampal neurons of aged humans, which is aggravated in AD patients. A similar profile of A2AR overexpression in rats was sufficient to drive age-like memory impairments in young animals and to uncover a hippocampal LTD-to-LTP shift. This was accompanied by increased NMDA receptor gating, dependent on mGluR5 and linked to enhanced Ca2+ influx. We confirmed the same plasticity shift in memory-impaired aged rats and APP/PS1 mice modeling AD, which was rescued upon A2AR blockade. This A2AR/mGluR5/NMDAR interaction might prove a suitable alternative for regulating aberrant mGluR5/NMDAR signaling in AD without disrupting their constitutive activity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
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Receptores de N-Metil-D-Aspartato
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Depressão Sináptica de Longo Prazo
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Receptor A2A de Adenosina
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Receptor de Glutamato Metabotrópico 5
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Neurônios
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Psychiatry
Assunto da revista:
BIOLOGIA MOLECULAR
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PSIQUIATRIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Portugal