title: GluN2D subunit-containing NMDA receptors control tissue plasminogen activator-mediated spatial memory.
abstract: Tissue plasminogen activator (tPA) is a serine protease with pleiotropic actions in the CNS, such as synaptic plasticity and neuronal death. Some effects of tPA require its interaction with the GluN1 subunit of the NMDA receptor (NMDAR), leading to a potentiation of NMDAR signaling. We have reported previously that the pro-neurotoxic effect of tPA is mediated through GluN2D subunit-containing NMDARs. Thus, the aim of the present study was to determine whether GluN2D subunit-containing NMDARs drive tPA-mediated cognitive functions. To address this issue, a strategy of immunization designed to prevent the in vivo interaction of tPA with NMDARs and GluN2D-deficient mice were used in a set of behavioral tasks. Altogether, our data provide the first evidence that tPA influences spatial memory through its preferential interaction with GluN2D subunit-containing NMDARs.
authors.affiliation: Inserm, Mixed Research Unit in Health U919, University Caen Basse Normandie, Serine Proteases and Pathophysiology of the Neurovascular Unit, Public Interest Group CYCERON, F-14074 Caen, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Obiang
authors.forename: Richard
authors.initials: R
authors.lastname: Macrez
authors.forename: Amandine
authors.initials: A
authors.lastname: Jullienne
authors.forename: Thomas
authors.initials: T
authors.lastname: Bertrand
authors.forename: Flavie
authors.initials: F
authors.lastname: Lesept
authors.forename: Carine
authors.initials: C
authors.lastname: Ali
authors.forename: Eric
authors.initials: E
authors.lastname: Maubert
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
authors.forename: Véronique
authors.initials: V
authors.lastname: Agin
mesh_terms: D000818:Animals; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013028:Space Perception / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D010959:Tissue Plasminogen Activator