These authors equally participated in this work.
Retinoids and glucocorticoids target common genes in hippocampal HT22 cells
Article first published online: 6 MAR 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 125, Issue 4, pages 518–531, May 2013
How to Cite
J. Neurochem.(2013) 125, 518–531.
- Issue published online: 25 APR 2013
- Article first published online: 6 MAR 2013
- Accepted manuscript online: 8 FEB 2013 12:00AM EST
- Manuscript Accepted: 14 JAN 2013
- Manuscript Revised: 11 JAN 2013
- Manuscript Received: 15 NOV 2012
- Conseil Régional d'Aquitaine
- brain neurotrophic factor;
- retinoic acid;
- retinoic acid receptor;
- tissue transglutaminase 2
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.