Impaired Locomotion and Dopamine Signaling in Retinoid Receptor Mutant Mice

El, Wojciech Krȩ Ż; Ghyselinck, Norbert B.; Samad, Tarek A.; Dupé, Valérie; Kastner, Philippe; Borrelli, Emiliana; Chambon, Pierre

doi:10.1126/science.279.5352.863

Cited by 320 publications

(266 citation statements)

References 26 publications

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“…Indications of a behavioral phenotype resulting from inhibition of RA signaling in the striatum come from studies of double null mutation of RARbeta with either RXRbeta or RXRgamma. Such mutations result in impaired locomotion typical of abnormal striatal function and possibly related to a decrease in the dopamine D1 and D2 type receptors in striatal neurons (Krezel et al 1998). Although it is possible that the phenotype of these RA receptor null mutations is due to a developmental effect the high expression of RA signaling components in the adult striatum suggests that an influence on adult function may be a significant component.…”

Section: Retinoic Acid Signaling In the Corpus Striatum And Nucleus Amentioning

confidence: 99%

“…Clearly RA can promote dopaminergic signaling in the embryo, but the influence of RA on the adult brain is uncertain. Null mutation of RA receptors results in a decrease in dopamine signaling however this effect may result from lack of embryonic development of the dopamine signaling system (Krezel et al 1998). If the effects of RA in the adult are similar to that in the embryo then this indicates that RA influences a system associated with depression; however the direction of its effect on gene expression within the dopaminergic system is the opposite to what would be expected for an agent that promotes depression.…”

Section: Relationship Between Ra and Dopaminementioning

confidence: 99%

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The neurobiology of retinoic acid in affective disorders

Bremner

McCaffery

2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

142

151

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Current models of affective disorders implicate alterations in norepinephrine, serotonin, dopamine, and CRF/cortisol; however treatments targeted at these neurotransmitters or hormones have led to imperfect resolution of symptoms, suggesting that the neurobiology of affective disorders is incompletely understood. Until now retinoids have not been considered as possible contributors to affective disorders. Retinoids represent a family of compounds derived from Vitamin A that perform a large number of functions, many via the vitamin A product, retinoic acid. This signaling molecule binds to specific retinoic acid receptors in the brain which, like the glucocorticoid and thyroid hormone receptors, are part of the nuclear receptor superfamily and regulate gene transcription. Research in the field of retinoic acid in the CNS has focused on the developing brain, in part stimulated by the observation that isotretinoin (13-cis retinoic acid), an isomer of retinoic acid used in the treatment of acne, is highly teratogenic for the CNS. More recent work has suggested that retinoic acid may influence the adult brain; animal studies indicated that the administration of isotretinoin is associated with alterations in behavior as well as inhibition of neurogenesis in the hippocampus. Clinical evidence for an association between retinoids and depression includes case reports in the literature, studies of health care databases, and other sources. A preliminary PET study in human subjects showed that isotretinoin was associated with a decrease in orbitofrontal metabolism. Several studies have shown that the molecular components required for retinoic acid signaling are expressed in the adult brain ; the overlap of brain areas implicated in retinoic acid function and stress and depression suggest that retinoids could play a role in affective disorders. This report reviews the evidence in this area and describes several systems that may be targets of retinoic acid and which contribute to the pathophysiology of depression.

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Section: Retinoic Acid Signaling In the Corpus Striatum And Nucleus Amentioning

confidence: 99%

Section: Relationship Between Ra and Dopaminementioning

confidence: 99%

The neurobiology of retinoic acid in affective disorders

Bremner

McCaffery

2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

142

151

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“…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. Interestingly, it has been previously shown that genetic ablation (KO) of the RXRg gene also produces a blunted cataleptic behavior in response to dopamine antagonist (Saga et al, 1999) and an altered Nuclear receptors and neuroleptic effects I Éthier et al enkephalin gene expression in the striatum (Krezel et al, 1998). Based on these considerations, it is tempting to suggest that both NGFI-B and RXR, possibly as a transcriptional complex, may be involved in the signaling cascade induced by haloperidol.…”

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

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

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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.

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“…Several reports have described isotretinoin effect on the rodent central nervous system (Ferguson et al, 2005;O'Reilly et al, 2006). Identification of retinoid receptors in various brain regions of adult animals indicated a functional role for retinoic acid in adult (Krezel et al, 1998;Le Dose et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Studies in mice and rats indicated that retinoid cross the blood brain barrier into central nervous system (Le Dose et al, 2000) and their receptors were found in adults brain, they may alter neural pathway such as dopamine signaling, which was known to be involved in mood and thought disorders (Krezel et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Neurotransmitters Level in Hypothyroid Male Albino Rats after Isotretinoin Treatment

El-Anwar¹,

Wahman²,

Melek³

2015

J. of Medical Sciences

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Isotretinoin is the most effective anti-acne treatment but to some extent it has side effects. So, the aim of the present study was focused on the combined effect of isotretinoin treatment and hypothyroidism on cerebral monoamines in male albino rats. The animals were divided into four groups; control, hypothyroid, hypothyroid treated with isotretinoin and isotretinoin only treated. Hypothyroidism was induced by using 5 mg kgG 1 propylthiouracil for 30 days. Oral isotretinoin was given in olive oil 1.5 mg kgG 1 b.wt. equivalent to human therapeutic dose for 4 weeks. The withdrawal period is 2 weeks after drug stoppage. The concentration of epinephrine, nor epinephrine, dopamine and serotonin were estimated in different brain areas. Also, the serum level of free triiodothyronine and free thyroxin and thyroid stimulating hormone were measured to insure the hypothyroid state. Total body weight was recorded throughout the experimental period. Hypothyroid rat's model exhibited a decrease of norepinephrine, dopamine and serotonin contents in most of the brain areas examined. Hypothyroid rats treated with isotretinoin exhibited elevated levels of neurotransmitter in most brain areas. isotretinoin treatment does not aggravate the monoamines dysfunction in hypothyroid rats.

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Impaired Locomotion and Dopamine Signaling in Retinoid Receptor Mutant Mice

Cited by 320 publications

References 26 publications

The neurobiology of retinoic acid in affective disorders

The neurobiology of retinoic acid in affective disorders

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

Neurotransmitters Level in Hypothyroid Male Albino Rats after Isotretinoin Treatment

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