The role of parkinson's disease‐associated receptor GPR37 in the hippocampus: functional interplay with the adenosinergic system
Abstract
GPR37 is an orphan G protein‐coupled receptor mostly enriched in brain areas such as the cerebellum, striatum, and hippocampus. Identified as a substrate of parkin, GPR37 has been suggested to play a role in Parkinson's disease. Distributed throughout the brain, the function of GPR37, however, remains unknown. We now provide the first mapping of GPR37 within the hippocampus, where GPR37 is widely expressed and localized at the level of the extrasynaptic plasma membrane of dendritic spines, dendritic shafts, and axon terminals. GPR37 per se does not appear to play a role in learning and memory, since knocking out GPR37 (GPR37‐KO) did not alter the performance in different hippocampal‐related memory tasks. This is in agreement with slice electrophysiology experiments showing no differences both in short‐term plasticity paired‐pulse facilitation and long‐term potentiation between WT and GPR37‐KO mice. However, we report a potential functional interaction between GPR37 and adenosine A2A receptors (A2AR) in the hippocampus, with A2AR modulating the GPR37‐associated phenotype. Thus, the absence of GPR37 appeared to sensitize mice to hippocampal A2AR‐mediated signaling, as observed by the effect of the A2AR antagonist SCH58261 increasing synaptic depotentiation, reducing novel object recognition memory and reverting the anxiolytic effect of GPR37 deletion. Collectively, these findings afford insight into the localization and role of the orphan GPR37 within the hippocampus with potential involvement in A2AR function (i.e., A2AR sensitization). image GPR37 is an orphan G protein‐coupled receptor widely expressed in the hippocampus and localized at the level of the extrasynaptic plasma membrane of dendritic spines, dendritic shafts and axon terminals. This orphan receptor per se does not appear to directly control the learning and memory processes; however knocking‐out GPR37 triggers anxiolytic‐like effects and sensitizes mice to hippocampal A2AR‐mediated signalling.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 21, 2015
- Source ID
- 10.1111/jnc.13109
Entities
People
- Carolina Souza
- Cindy Pinhal
- Francisco Ciruela
- Henrique B. Silva
- Igor Stagljar
- Jorge Gandía
- João P. Lopes
- Nuno J. Machado
- Paula M. Canas
- Rafael Luján
- Rodrigo A. Cunha
- Víctor Fernández‐dueñas
- Xavier Morató
Organizations
- Agency for Innovation by Science and Technology
- Bellvitge Biomedical Research Institute
- Brain & Behavior Research Foundation
- Catalan Institution for Research and Advanced Studies
- Defense Advanced Research Projects Agency
- Fundação para a Ciência e Tecnologia
- Ghent University
- University of Coimbra
- University of Toronto