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Science 290 (5499): 2140-2144

Copyright © 2000 by the American Association for the Advancement of Science

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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C. Stehlin, J.-M. Wurtz, A. Steinmetz, E. Greiner, R. Schule, D. Moras, and J.-P. Renaud (2001)
EMBO J. 20, 5822-5831
   Abstract »    Full Text »    PDF »
Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity.
D. L. Misner, S. Jacobs, Y. Shimizu, A. M. de Urquiza, L. Solomin, T. Perlmann, L. M. De Luca, C. F. Stevens, and R. M. Evans (2001)
PNAS 98, 11714-11719
   Abstract »    Full Text »    PDF »
Docosahexaenoic acid synthesis from n-3 polyunsaturated fatty acids in differentiated rat brain astrocytes.
D. E. Williard, S. D. Harmon, T. L. Kaduce, M. Preuss, S. A. Moore, M. E. C. Robbins, and A. A. Spector (2001)
J. Lipid Res. 42, 1368-1376
   Abstract »    Full Text »    PDF »
Active repression of RAR signaling is required for head formation.
T. Koide, M. Downes, R. A.S. Chandraratna, B. Blumberg, and K. Umesono (2001)
Genes & Dev. 15, 2111-2121
   Abstract »    Full Text »    PDF »
Delivery and turnover of plasma-derived essential PUFAs in mammalian brain.
S. I. Rapoport, M. C. J. Chang, and A. A. Spector (2001)
J. Lipid Res. 42, 678-685
   Abstract »    Full Text »
The structure of the ultraspiracle ligand-binding domain reveals a nuclear receptor locked in an inactive conformation.
G. M. Clayton, S. Y. Peak-Chew, R. M. Evans, and J. W. R. Schwabe (2001)
PNAS 98, 1549-1554
   Abstract »    Full Text »    PDF »
The structure of the ultraspiracle ligand-binding domain reveals a nuclear receptor locked in an inactive conformation.
G. M. Clayton, S. Y. Peak-Chew, R. M. Evans, and J. W. R. Schwabe (2001)
PNAS
   Abstract »    Full Text »
Hydrophobic Ligand Binding by Zn-alpha 2-glycoprotein, a Soluble Fat-depleting Factor Related to Major Histocompatibility Complex Proteins.
M. W. Kennedy, A. P. Heikema, A. Cooper, P. J. Bjorkman, and L. M. Sanchez (2001)
J. Biol. Chem. 276, 35008-35013
   Abstract »    Full Text »    PDF »
The Orphan Nuclear Receptor LRH-1 Potentiates the Sterol-mediated Induction of the Human CETP Gene by Liver X Receptor.
Y. Luo, C.-p. Liang, and A. R. Tall (2001)
J. Biol. Chem. 276, 24767-24773
   Abstract »    Full Text »    PDF »
The structure of the ultraspiracle ligand-binding domain reveals a nuclear receptor locked in an inactive conformation.
G. M. Clayton, S. Y. Peak-Chew, R. M. Evans, and J. W. R. Schwabe (2001)
PNAS
   Abstract »    Full Text »
Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity.
D. L. Misner, S. Jacobs, Y. Shimizu, A. M. de Urquiza, L. Solomin, T. Perlmann, L. M. De Luca, C. F. Stevens, and R. M. Evans (2001)
PNAS 98, 11714-11719
   Abstract »    Full Text »    PDF »

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