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Science 15 December 2000:
Vol. 290. no. 5499, pp. 2140 - 2144
DOI: 10.1126/science.290.5499.2140
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Reports

Docosahexaenoic Acid, a Ligand for the Retinoid X Receptor in Mouse Brain

Alexander Mata de Urquiza,1 Suya Liu,2* Maria Sjöberg,3* Rolf H. Zetterström,1 William Griffiths,2 Jan Sjövall,2 Thomas Perlmann1dagger

The retinoid X receptor (RXR) is a nuclear receptor that functions as a ligand-activated transcription factor. Little is known about the ligands that activate RXR in vivo. Here, we identified a factor in brain tissue from adult mice that activates RXR in cell-based assays. Purification and analysis of the factor by mass spectrometry revealed that it is docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid that is highly enriched in the adult mammalian brain. Previous work has shown that DHA is essential for brain maturation, and deficiency of DHA in both rodents and humans leads to impaired spatial learning and other abnormalities. These data suggest that DHA may influence neural function through activation of an RXR signaling pathway.

1 Ludwig Institute for Cancer Research, Stockholm Branch, Box 240, S-171 77 Stockholm, Sweden.
2 Department of Medical Chemistry and
3 Department of Cell and Molecular Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: thomas.perlmann{at}licr.ki.se

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