Retinoids and glucocorticoids target common genes in hippocampal HT22 cells.
J. Neurochem.. 2013-03-06; 125(4): 518-531
DOI: 10.1111/jnc.12192
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1. J Neurochem. 2013 May;125(4):518-31. doi: 10.1111/jnc.12192. Epub 2013 Mar 6.
Retinoids and glucocorticoids target common genes in hippocampal HT22 cells.
Brossaud J(1), Roumes H, Moisan MP, Pallet V, Redonnet A, Corcuff JB.
Author information:
(1)INRA, Nutrition et Neurobiologie Intégrée, UMR1286, Bordeaux, France.
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.
© 2013 International Society for Neurochemistry.
DOI: 10.1111/jnc.12192
PMID: 23398290 [Indexed for MEDLINE]