title: Retinoids and glucocorticoids target common genes in hippocampal HT22 cells.
abstract: Vitamin A metabolite retinoic acid (RA) plays a major role in the aging adult brain plasticity. Conversely, chronic excess of glucocorticoids (GC) elicits some deleterious effects in the hippocampus. We questioned here the involvement of RA and GC in the expression of target proteins in hippocampal neurons. We investigated proteins involved either in the signaling pathways [RA receptor β (RARβ) and glucocorticoid receptor (GR)] or in neuron differentiation and plasticity [tissue transglutaminase 2 (tTG) and brain-derived neurotrophic factor (BDNF)] in a hippocampal cell line, HT22. We applied RA and/or dexamethasone (Dex) as activators of the pathways and investigated mRNA and protein expression of their receptors and of tTG and BDNF as well as tTG activity and BDNF secretion. Our results confirm the involvement of RA- and GC-dependent pathways and their interaction in our neuronal cell model. First, both pathways regulate the transcription and expression of own and reciprocal receptors: RA and Dex increased RARβ and decreased GR expressions. Second, Dex reduces the expression of tTG when associated with RA despite stimulating its expression when used alone. Importantly, when they are combined, RA counteracts the deleterious effect of glucocorticoids on BDNF regulation and thus may improve neuronal plasticity under stress conditions. In conclusion, GC and RA both interact through regulations of the two receptors, RARβ and GR. Furthermore, they both act, synergistically or oppositely, on other target proteins critical for neuronal plasticity, tTG and BDNF.
authors: INRA, Nutrition et Neurobiologie Intégrée, UMR1286, Bordeaux, France.
authors: Julie
authors: J
authors: Brossaud
authors: Hélène
authors: H
authors: Roumes
authors: Marie-Pierre
authors: MP
authors: Moisan
authors: Véronique
authors: V
authors: Pallet
authors: Anabelle
authors: A
authors: Redonnet
authors: Jean-Benoît
authors: JB
authors: Corcuff
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D009336:Necrosis; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D014212:Tretinoin; D003907:Dexamethasone; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins