title: NMDA-induced ERK signalling is mediated by NR2B subunit in rat cortical neurons and switches from positive to negative depending on stage of development.
abstract: It is known that NMDA receptor stimulation can activate or inhibit the extracellular signal-regulated kinase (ERK) signalling cascade, a key pathway involved in neuronal plasticity and survival. However, the specific subtype(s) of NMDA receptor that exert bi-directional regulation of ERK signalling is under debate. Here we show that in young neurons (7-9 days in vitro, DIV), NMDA activated ERK signalling. In mature neurons (14-16 DIV), NMDA-evoked, in coincidence with a concentration-dependent increase in intracellular Ca(2+) ([Ca(2+)](i)), an increase in ERK phosphorylation at low concentrations (1-30 μM) while an inhibition at high concentrations (30 μM-250 μM). In more mature neurons (21-23 DIV) NMDA inhibited ERK signalling. Both activation and inhibition of ERK signalling were fully reversed by the selective NR2B receptor antagonists Ro 25-6981 and ifenprodil. Thus, the NR2B subunit can be both negatively or positively coupled to ERK signalling in rat cortical neurons, depending on their stage of development. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
authors: Department of Molecular and Cellular Biology, Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline R&D, 37135 Verona, Italy. anna.sava@aptuit.com
authors: Anna
authors: A
authors: Sava
authors: Elena
authors: E
authors: Formaggio
authors: Corrado
authors: C
authors: Carignani
authors: Filippo
authors: F
authors: Andreetta
authors: Ezio
authors: E
authors: Bettini
authors: Cristiana
authors: C
authors: Griffante
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D048049:Extracellular Signal-Regulated MAP Kinases