Details

Autor(en) / Beteiligte

• Temido-Ferreira, Mariana
• Ferreira, Diana G
• Batalha, Vânia L
• Marques-Morgado Inês
• Coelho, Joana E
• Pereira, Pedro
• Gomes, Rui
• Pinto Andreia
• Carvalho, Sara
• Canas, Paula M
• Cuvelier Laetitia
• Buée-Scherrer Valerie
• Faivre Emilie
• Younis, Baqi
• Müller, Christa E
• Pimentel José
• Schiffmann, Serge N
• Buée Luc
• Bader, Michael
• Outeiro, Tiago F
• Blum, David
• Cunha, Rodrigo A
• Marie, Hélène
• Pousinha, Paula A
• Lopes, Luísa V

Titel

Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors

Ist Teil von

• Molecular psychiatry, 2020-08, Vol.25 (8), p.1876-1900

Ort / Verlag

New York: Nature Publishing Group

Erscheinungsjahr

2020

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.