Retinoid x receptor gamma is implicated in docosahexaenoic acid modulation of despair behaviors and working memory in mice.

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Wietrzych-Schindler M, Szyszka-Niagolov M, Ohta K, Endo Y, Perez E, de Lera AR, Chambon P, Krezel W

Retinoid x receptor gamma is implicated in docosahexaenoic acid modulation of despair behaviors and working memory in mice.

Biol Psychiatry. 2011 Apr 15;69(8):788-94. doi: 10.1016/j.biopsych.2010.12.017. Epub 2011 Feb 21.

PubMed ID

21334601 [ View in PubMed

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Abstract

BACKGROUND: Omega-3 polyunsaturated fatty acids, including docosahexaenoic acid (DHA), have antidepressant and promnemonic functions. The mechanisms of such activities are still elusive and may involve retinoid X receptors (RXRs), transcription factors known to bind DHA in vitro. METHODS: Promnemonic and antidespair activities of acute DHA treatment were tested in BALBcByJ mice using spontaneous alternation and forced swim test, respectively. The involvement of retinoid receptors in such DHA activities was investigated using RXR and/or retinoic acid receptor (RAR) agonists to mimic DHA activities or a synthetic pan-RXR antagonist to block them. Involvement of RXR isotypes was analyzed using the same tasks and delayed nonmatch to place for working memory in RXRgamma knockout mice. RESULTS: Docosahexaenoic acid decreased despair behavior and improved working memory in BALBcByJ mice. Such effects were suppressed by co-treatment with BR1211, a pan-RXR antagonist, whereas a pan-RXR agonist, UVI2108, mimicked DHA activities. Retinoic acid (RA), a natural ligand of RXRs, also reduced despair behavior and improved working memory and such activities did not require activation of RARs, as RA effects were abolished by co-treatment with BR1211 and they were not reproduced by TTNPB, a pan-RAR agonist. The RXRgamma knockout mice displayed increased despair and deficits in working memory, which were insensitive to DHA and pan-RXR agonist treatments, whereas DHA or UVI2108 reversed these deficits in RXRgamma heterozygous mice. CONCLUSIONS: Our data suggest that RXRs are a converging point in mediating DHA and RA modulations of despair behavior and working memory and that RXRgamma is the predominant RXR isotype in these regulations.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Doconexent	Retinoic acid receptor RXR-gamma	Protein	Humans	Yes	Activator	Details