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NMDA receptor activation decreases adenosine A 2A R function in APP SW,IND animal model of Alzheimer disease
Author(s) -
Navarro Gemma,
Reyes Irene,
Raïch Iu,
Marquez Alejandro Lillo,
Del Ser Anna,
Casanovas Mireia,
Saura Carles,
Franco Rafael
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.037667
Subject(s) - nmda receptor , excitotoxicity , microglia , agonist , glutamate receptor , chemistry , neuroinflammation , receptor , microbiology and biotechnology , neuroscience , pharmacology , biology , biochemistry , immunology , inflammation
Background Etiology of Alzheimer's disease (AD) remain unclear. Different pathological processes have been descrived, such as phosphorylation of tau protein, amyloid plaques, oxidative stress or neuroinflammation. It has been described that over‐activation of the NMDA receptor due to an increase in glutamate levels induces excitotoxicity in neurodegenerative disorders, on the other hand, these disorders course with a chronic neuroinflamation where adenosine A 2A receptor play an important role. Methods Energy transfer techniques have been assayed to determine protein‐protein interactions. Different signaling pathways have been analyzed, such as MAPK phosphorylation (determined using AlphaScreen ® SureFire ® kit (Perkin Elmer), calcium release (detected with the GCaMP6 calcium sensor) or Dynamic Mass Redistribution (analyzed by label‐free‐DMR technology). Finally, determination of heteromer expression level has been performed by Proximity ligation assay (PLA). Result It has been observed that in LPS activated microglia primary cultures of control mice and also in microglia from APP Sw,Ind mice model of AD, NMDA activation inhibit A 2A R signalling, decreasing the proinflamatory effects evoked by A 2A R stimulation. This inhibition of NMDA receptor over A 2A R is characteristic of microglia cells but is only partial in neuronal primary cultures where there is a lower expression of A 2A ‐NMDA receptor complexes. Conclusion NMDA receptor activation decrease the selective A 2A receptor agonist, CGS21680, induced effects in neuronal and microglial primary cultures of APP Sw,Ind mice model of AD.