title: Molecular characterization of the AMPA-receptor potentiator S70340 in rat primary cortical culture: whole-genome expression profiling.
abstract: To improve our understanding of the molecular events underlying the effects of positive allosteric modulators of the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (S)-AMPA-type glutamate receptors, gene expression profiles of primary cortical culture were measured by Agilent-Microarray technique under (S)-AMPA (1μM) stimulation for 0.5, 6, 24 and 48h in the presence or absence of S70340 (30μM), an allosteric potentiator of AMPA receptors. (S)-AMPA and S70340 treatment alone have little effect on gene expression whereas as early as 6h, their combination induced a large number of genes known to decrease apoptosis and mediate cell survival. Pathway analyses of (S)-AMPA+S70340 treatment-mediated gene expression from 6 to 48h further suggested the activation of cellular functions including neuron differentiation and neurite outgrowth. A proportion of genes implicated in these functions encode proteins involved in environmental cues and are expressed in growth cones, such as extracellular matrix component proteins and filopodia microfilament-associated proteins. Time course analysis of mRNA expression combined with in silico promoter analysis revealed an enrichment in the cAMP response element (CRE) among co-regulated genes. This study demonstrated that S70340-mediated AMPA potentialisation activated genes and functional processes involved in neuroprotective and cognitive effects and describes putative new functional biomarkers.
authors: Institut de Recherche Servier, 125 chemin de ronde, 78290 Croissy-sur-Seine, France.
authors: Sophie
authors: S
authors: Mourlevat
authors: Jean-Pierre
authors: JP
authors: Galizzi
authors: Nolwen
authors: N
authors: Guigal-Stéphan
authors: Sophie
authors: S
authors: Courtade-Gaïani
authors: Gaëlle
authors: G
authors: Rolland-Valognes
authors: Marianne
authors: M
authors: Rodriguez
authors: Fabienne
authors: F
authors: Barbet
authors: Chantal
authors: C
authors: Bourrier
authors: Sandra
authors: S
authors: Catesson
authors: Agnès
authors: A
authors: Chomel
authors: Laurence
authors: L
authors: Danober
authors: Nadège
authors: N
authors: Villain
authors: Daniel-Henry
authors: DH
authors: Caignard
authors: Bernard
authors: B
authors: Pirotte
authors: Pierre
authors: P
authors: Lestage
authors: Brian Paul
authors: BP
authors: Lockhart