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Triiodothyronine administration reverses vitamin A deficiency-related hypo-expression of retinoic acid and triiodothyronine nuclear receptors and of neurogranin in rat brain

Published online by Cambridge University Press:  07 June 2007

Marianne Husson
Affiliation:
Unité de Nutrition et Signalisation Cellulaire (E.A. MENRT; USC INRA) ISTAB, Université Bordeaux 1, Avenue des Facultés, 33405 Talence cedex, France
Valérie Enderlin
Affiliation:
Unité de Nutrition et Signalisation Cellulaire (E.A. MENRT; USC INRA) ISTAB, Université Bordeaux 1, Avenue des Facultés, 33405 Talence cedex, France
Serge Alfos
Affiliation:
Unité de Nutrition et Signalisation Cellulaire (E.A. MENRT; USC INRA) ISTAB, Université Bordeaux 1, Avenue des Facultés, 33405 Talence cedex, France
Catherine Féart
Affiliation:
Unité de Nutrition et Signalisation Cellulaire (E.A. MENRT; USC INRA) ISTAB, Université Bordeaux 1, Avenue des Facultés, 33405 Talence cedex, France
Paul Higueret
Affiliation:
Unité de Nutrition et Signalisation Cellulaire (E.A. MENRT; USC INRA) ISTAB, Université Bordeaux 1, Avenue des Facultés, 33405 Talence cedex, France
Véronique Pallet*
Affiliation:
Unité de Nutrition et Signalisation Cellulaire (E.A. MENRT; USC INRA) ISTAB, Université Bordeaux 1, Avenue des Facultés, 33405 Talence cedex, France
*
*Corresponding author: Dr Véronique Pallet, fax +33 5 56 84 27 76, email v.pallet@istab.u-bordeaux1.fr
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Abstract

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Recent studies have revealed that retinoids play an important role in the adult central nervous system and cognitive functions. Previous investigations in mice have shown that vitamin A deficiency (VAD) generates a hypo-expression of retinoic acid (RA, the active metabolite of vitamin A) receptors and of neurogranin (RC3, a neuronal protein involved in synaptic plasticity) and a concomitant selective behavioural impairment. Knowing that RC3 is both a triiodothyronine (T3) and a RA target gene, and in consideration of the relationships between the signalling pathways of retinoids and thyroid hormones, the involvement of T3 on RA signalling functionality in VAD was investigated. Thus, the effects of vitamin A depletion and subsequent administration with RA and/or T3 on the expression of RA nuclear receptors (RAR, RXR), T3 nuclear receptor (TR) and on RC3 in the brain were examined. Rats fed a vitamin A-deficient diet for 10 weeks exhibited a decreased expression of RAR, RXR and TR mRNA and of RC3 mRNA and proteins. RA administration to these vitamin A-deficient rats reversed only the RA hypo-signalling in the brain. Interestingly, T3 is able to restore its own brain signalling simultaneously with that of vitamin A and the hypo-expression of RC3. These results obtained in vivo revealed that one of the consequences of VAD is a dysfunction in the thyroid signalling pathway in the brain. This seems of crucial importance since the down regulation of RC3 observed in the depleted rats was corrected only by T3.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2003

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