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

Urquiza, Alexander Mata de; Liu, Suya; Sjöberg, Maria; Zetterström, Rolf; Griffiths, William J.; Sjövall, Jan; Perlmann, Thomas

doi:10.1126/science.290.5499.2140

Cited by 683 publications

(431 citation statements)

References 42 publications

Supporting

Mentioning

411

Contrasting

Unclassified

Order By: Relevance

“…We show here that haloperidol administration strongly increase the percentage of colocalization of NGFI-B and RXRg1 transcripts in the striatum. In addition, coadministration with haloperidol of two retinoid ligands, 9-cis RA and DHA (Heyman et al, 1992;de Urquiza et al, 2000), dose-dependently reduced or suppressed haloperidol-induced catalepsy and enkephalin mRNA upregulation. Although the enkephalin gene promoter contains a retinoic acid responsive element (RARE) , the activity of NGFI-B on the enkephalin promoter activity is not known.…”

Section: Ngfi-b(+/+) Ngfi-b(-/-) Ngfi-b(+/+) Ngfi-b(-/mentioning

confidence: 93%

“…It has been previously shown that 9-cis RA strongly enhances the transcriptional activity of the NGFI-B/RXR heterodimer in vitro ( Nuclear receptors and neuroleptic effects I Éthier et al Vivat et al, 1997). More recently, DHA has been identified as a natural ligand for retinoid receptors (de Urquiza et al, 2000;Egea et al, 2002). Administration of 9-cis RA in combination with haloperidol dose-dependently reduces the severity of drug-induced catalepsy (Figure 6a, b), whereas it has no behavioral effect when injected alone (Figure 6a).…”

Section: Retinoid Ligands Can Suppress Haloperidol-induced Catalepsymentioning

confidence: 99%

See 1 more Smart Citation

The Transcription Factor NGFI-B (Nur77) and Retinoids Play a Critical Role in Acute Neuroleptic-Induced Extrapyramidal Effect and Striatal Neuropeptide Gene Expression

Éthier

Beaudry

St-Hilaire

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

Despite extensive investigation, the cellular mechanisms responsible for neuroleptic actions remain elusive. We have previously shown that neuroleptics modulated the expression of some members of the ligand-activated transcription factors (nuclear receptors) including the nerve-growth factor inducible gene B (NGFI-B or Nur77) and retinoid X receptor (RXR) isoforms. Using genetic and pharmacological approaches, we investigated the role of NGFI-B and retinoids in acute behavioral and biochemical responses to dopamine antagonists. NGFI-B knockout (KO) mice display a profound alteration of haloperidol-induced catalepsy and striatal neuropeptide gene expression. Haloperidol-induced increase of striatal enkephalin mRNA is totally abolished in NGFI-B KO mice whereas the increase of neurotensin mRNA expression is reduced by 50%. Interestingly, catalepsy induced by raclopride, a specific dopamine D 2 /D 3 antagonist is completely abolished in NGFI-B-deficient mice whereas the cataleptic response to SCH 23390, a dopamine D 1 agonist, is preserved. Accordingly, the effects of haloperidol on striatal c-fos, Nor-1, and dynorphin mRNA expression are also preserved in NGFI-B-deficient mice. The cataleptic response and the increase of enkephalin mRNA expression induced by haloperidol can also be suppressed by administration of retinoid ligands 9-cis retinoic acid and docosahexaenoic acid. In addition, we demonstrate that haloperidol enhances colocalization of NGFI-B and RXRg1 isoform mRNAs, suggesting that both NGFI-B and a RXR isoform are highly coexpressed after haloperidol administration. Our data demonstrate, for the first time, that NGFI-B and retinoids are actively involved in the molecular cascade induced by neuroleptic drugs.

show abstract

Section: Ngfi-b(+/+) Ngfi-b(-/-) Ngfi-b(+/+) Ngfi-b(-/mentioning

confidence: 93%

Section: Retinoid Ligands Can Suppress Haloperidol-induced Catalepsymentioning

confidence: 99%

The Transcription Factor NGFI-B (Nur77) and Retinoids Play a Critical Role in Acute Neuroleptic-Induced Extrapyramidal Effect and Striatal Neuropeptide Gene Expression

Éthier

Beaudry

St-Hilaire

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Among the transcription factors known to bind to DHA are the peroxisome proliferatoractivated receptors (PPAR) (56) and the retinoic acid X nuclear receptor (57). The interaction with PPAR may be potentially important because of these transcription factors' role in regulating inflammation (58).…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic Acid Ameliorates Murine Ischemic Acute Renal Failure and Prevents Increases in mRNA Abundance for both TNF-α and Inducible Nitric Oxide Synthase

Kielar¹,

Jeyarajah²,

Zhou³

et al. 2003

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Abstract. This study demonstrates that intraperitoneal injections of DHA (all cis 4,7,10,13,16,19 docosahexaenoic acid C22: n-3) bound to bovine serum albumin ameliorate murine acute renal failure (ARF) induced by temporary occlusion of the renal artery. Three micromoles of DHA decreased serum creatinine (Scr) from 2.3 mg/dl to 1.1 mg/dl 24 h after reperfusion (n ϭ 15; P Ͻ 0.05). Scr of the treated animals were significantly lower than controls throughout a 7-d time course. Although lower doses of DHA were less effective, higher doses were not more effective. Ribonuclease (RNase) protection assays showed that ischemia increased mRNA abundance for TNF-␣ and inducible nitric oxide synthase (iNOS) at 24 h. This increase was prevented by DHA administration. Because TNF-␣ and iNOS contribute to renal ischemic injury, their inhibition may contribute to DHA's salutary effect. In addition, the data may have therapeutic implications, because the DHA improves ARF even when administered at 4 h after reperfusion.

show abstract

“…Because of its high degree of unsaturation, phospholipids containing this fatty acid may increase membrane fluidity and regulate the functions of membrane-associated proteins [90][91][92] . Docosahexaenoic acid itself may act as a signalling molecule by binding to retinoid X receptor (RXR), a ligand-activated transcription factor 93 (fIG. 5), or it may be oxygenated to produce various bioactive lipids.…”

Section: Signalling On Demandmentioning

confidence: 99%

A neuroscientist's guide to lipidomics

2007

View full text Add to dashboard Cite

| Nerve cells mould the lipid fabric of their membranes to ease vesicle fusion, regulate ion fluxes and create specialized microenvironments that contribute to cellular communication. The chemical diversity of membrane lipids controls protein traffic, facilitates recognition between cells and leads to the production of hundreds of molecules that carry information both within and across cells. With so many roles, it is no wonder that lipids make up half of the human brain in dry weight. The objective of neural lipidomics is to understand how these molecules work together; this difficult task will greatly benefit from technical advances that might enable the testing of emerging hypotheses.

show abstract

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

Cited by 683 publications

References 42 publications

The Transcription Factor NGFI-B (Nur77) and Retinoids Play a Critical Role in Acute Neuroleptic-Induced Extrapyramidal Effect and Striatal Neuropeptide Gene Expression

The Transcription Factor NGFI-B (Nur77) and Retinoids Play a Critical Role in Acute Neuroleptic-Induced Extrapyramidal Effect and Striatal Neuropeptide Gene Expression

Docosahexaenoic Acid Ameliorates Murine Ischemic Acute Renal Failure and Prevents Increases in mRNA Abundance for both TNF-α and Inducible Nitric Oxide Synthase

A neuroscientist's guide to lipidomics

Contact Info

Product

Resources

About