1. Molecular characterization of the AMPA-receptor potentiator S70340 in rat primary cortical culture: whole-genome expression profiling.
- Author
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Mourlevat S, Galizzi JP, Guigal-Stéphan N, Courtade-Gaïani S, Rolland-Valognes G, Rodriguez M, Barbet F, Bourrier C, Catesson S, Chomel A, Danober L, Villain N, Caignard DH, Pirotte B, Lestage P, and Lockhart BP
- Subjects
- Animals, Cells, Cultured, Cerebral Cortex drug effects, Gene Regulatory Networks genetics, Rats, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid analogs & derivatives, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid pharmacology, Cerebral Cortex physiology, Gene Expression Profiling methods, Genome-Wide Association Study methods, Receptors, AMPA agonists, Receptors, AMPA physiology
- 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., (Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)
- Published
- 2011
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