Bader M

Baqi Y

Batalha VL

Blum D

Buee L

Buee-Scherrer V

Canas PM

Carvalho S

Coelho JE

Cunha RA

Cuvelier L

Faivre E

Ferreira DG

Gomes R

Lopes LV

Marie H

Marques-Morgado I

Muller CE

Outeiro TF

Pereira P

Pimentel J

Pinto A

Pousinha PA

Schiffmann SN

Temido-Ferreira M

\ua9 2018 The Author(s). 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

Newcastle University E-Prints

Age-related shift in LTD is dependent on neuronal adenosine A<sub>2A</sub> receptors interplay with mGluR5 and NMDA receptors

https://eprint.ncl.ac.uk/fulltext.aspx?url=249649/8A9447F5-0D69-4A03-811B-778DBDD0BCBD.pdf&pub_id=249649

Age-related shift in LTD is dependent on neuronal adenosine A<sub>2A</sub> receptors interplay with mGluR5 and NMDA receptors

Abstract

Similar works

Full text

Available Versions

Newcastle University E-Prints