Volume 90, Issue 1, July (2003), pp. 191-198 © The Author 2003
doi:10.1079/BJN2003877

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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

Véronique Pallet¹, Marianne Husson¹, Valérie Enderlin¹, Serge Alfos¹, Catherine Féart¹, Paul Higueret^1
1Unité de Nutrition et Signalisation Cellulaire (E.A. MENRT; USC INRA) ISTAB, Université Bordeaux 1, Avenue des Facultés, 33405 Talence cedex, France

 (Received 7 May 2002–Revised 23 December 2002–Accepted 10 February 2003)

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.

Keywords:
Vitamin A deficiency, Retinoic acid nuclear receptors, Triiodothyronine nuclear receptors, Brain, Neurogranin

Abbreviations:
GAPDH, glyceraldehyde 3-phosphate dehydrogenase, PCR, polymerase chain reaction, RA, retinoic acid, RAR, retinoic acid receptor, RC3, neurogranin, RXR, retinoid X receptor, T₃, triiodothyronine, TR, triiodothyronine nuclear receptor, tTG, tissue-type transglutaminase, VAD, vitamin A deficiency