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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 ,
Valérie Enderlin ,
Serge Alfos ,
Catherine Féart ,
Paul Higueret  and
Véronique Pallet
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.

Keywords

Vitamin A deficiencyRetinoic acid nuclear receptorsTriiodothyronine nuclear receptorsBrainNeurogranin
Type
Research Article
Information
British Journal of Nutrition , Volume 90 , Issue 1 , July 2003 , pp. 191 - 198
Copyright
Copyright © The Nutrition Society 2003

References

Alfos, S, Higueret, P, Pallet, V, Higueret, D, Garcin, H & Jaffard, R (1996) Chronic ethanol consumption increases the amount of mRNA for retinoic acid and triiodothyronine receptors in mouse brain. Neurosci Lett 206, 73–76.CrossRefGoogle ScholarPubMed
Audouin-Chevallier, I, Higueret, P, Pallet, V, Higueret, D & Garcin, H (1993) Dietary vitamin A modulates the properties pf retinoic acid and glucocorticoid receptors in rat liver. Am Instit Nutr 123, 1195–1202.Google Scholar
Bradford, M (1976) A rapid and sensitive method for a quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248–254.CrossRefGoogle ScholarPubMed
Chambon, P (1996) A decade of molecular biology of retinoic acid receptors. FASEB J 10, 940–954.CrossRefGoogle ScholarPubMed
Chiang, MY, Misner, D & Kempermann, G, et al. (1998) An essential role for retinoid receptors RARβ and RXRγ in long-term potentiation and depression. Neuron 21, 1353–1361.CrossRefGoogle ScholarPubMed
Chin, WW & Yen, PM (1997) Molecular mechanisms of nuclear thyroid hormone action. In Contemporary Endocrinology: Diseases of the Thyroid. pp 1–10. [Braverman Humana, LE, editor]. Totowa, NJ: Press Inc..Google Scholar
Chiocca, EA, Davies, PJ & Stein, JP (1989) Regulation of tissue transglutaminase gene expression as a molecular model for retinoid effects on proliferation and differentiation. J Cell Biochem 39, 293–304.CrossRefGoogle ScholarPubMed
Chomczynski, P & Sacchi, N (1987) Single step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 162, 156–159.CrossRefGoogle Scholar
Cocco, S, Diaz, G & Stancampiano, R, et al. (2002) Vitamin A deficiency produces spatial learning and memory impairment in rats. Neuroscience 115, 475–482.CrossRefGoogle ScholarPubMed
Connor, MJ & Sidell, N (1997) Retinoic acid synthesis in normal and Alzheimer diseased brain and human neural cells. Mol Chem Neuropathol 30, 239–252.CrossRefGoogle ScholarPubMed
Enderlin, V, Higueret, D & Alfos, S, et al. (2000) Vitamin A deficiency decreases the expression of RARβ and RXRβ/γ in adult mouse brain: effect of RA administration. Nutr Neurosci 3, 173–181.CrossRefGoogle ScholarPubMed
Enderlin, V, Pallet, V & Alfos, S, et al. (1997) Age-related decreases in mRNA for brain nuclear receptors and target genes are reversed by retinoic acid treatment. Neurosci Lett 229, 125–129.CrossRefGoogle ScholarPubMed
Etchamendy, N, Enderlin, V, Marighetto, A, Pallet, V, Higueret, P & Jaffard, R (2000) Evidence for a role of vitamin A in higher cognitive functions. Society Neurosci Abstr 26, 1748.Google Scholar
Etchamendy, N, Enderlin, V & Marighetto, A, et al. (2001) Alleviation of a selective age-related relational memory deficit in mice by pharmacologically induced normalization of brain retinoid signaling. J Neurosci 21, 6423–6429.CrossRefGoogle ScholarPubMed
Gerendasy, DD & Sutcliffe, JG (1997) RC3/neurogranin, a postsynaptic calpacitin for setting the response threshold to calcium influxes. Mol Neurobiol 15, 131–163.CrossRefGoogle ScholarPubMed
Guadaño-Ferraz, A, Escamez, MJ, Morte, B, Vargiu, P & Bernal, J (1997) Transcriptional induction of RC3/neurogranin by thyroid hormone: differential neuronal sensitivity is not correlated with thyroid hormone receptor distribution in the brain. Mol Brain Res 49, 37–44.CrossRefGoogle Scholar
Higueret, P & Garcin, H (1982) Peripheral metabolism of thyroid hormones in vitamin A-deficient rats. Annals Nutr Metab 26, 191–200.CrossRefGoogle ScholarPubMed
Higueret, P & Garcin, H (1984) Triiodothyronine and vitamin A-deficiency in the rat. J Physiol (Paris) 79, 373–377.Google ScholarPubMed
Ingenbleek, Y & Bernstein, LH (1999) The nutritionally dependent adaptive dichotomy (NDAD) and stress hypermetabolism. J Clinical Ligand Assay 22, 259–267.Google Scholar
Ingenbleek, Y & De Visscher, M (1979) Hormonal and nutritional status: critical conditions for endemic goiter epidemiology?. Metabolism 28, 9–19.CrossRefGoogle ScholarPubMed
Iñiguez, MA, Morte, B & Rodriguez-Pena, A, et al. (1994) Characterization of the promoter region and flanking sequences of the neuron-specific gene RC3 (neurogranin). Brain Res Mol Brain Res 27, 205–214.CrossRefGoogle ScholarPubMed
Jeannin, E, Robyr, D & Desvergne, B (1998) Transcriptional regulatory patterns of the myelin basic protein and malic enzyme genes by the thyroid hormone receptors alpha1 and beta1. J Biol Chem 273, 24239–24248.CrossRefGoogle ScholarPubMed
Kastner, P, Mark, M & Chambon, P (1995) Nonsteroid nuclear receptors: what are genetic studies telling us about their role in real life?. Cell 83, 859–869.CrossRefGoogle ScholarPubMed
Környei, Z, Toth, B, Tretter, L & Madarasz, E (1999) Effects of retinoic acid on rat forebrain cells derived from embryonic and perinatal rats. Neurochem Int 33, 541–549.CrossRefGoogle Scholar
Krezel, W, Kastner, P & Chambon, P (1999) Differential expression of retinoid receptors in the adult mouse central nervous system. Neuroscience 89, 1291–1300.CrossRefGoogle ScholarPubMed
Leclercq, M & Bourgeay-Causse, M (1981) Une méthode simple, fiable rapide: dosage simultané du rétinol et du tocophérol sérique par chromatographie liquide haute performance (A simple, reliable fast method: simultaneous proportioning of retinol and serum tocopherol by high performance liquid chromatography). Revue Institut Pasteur Lyon 14, 475–496.Google Scholar
McCaffery, P & Dräger, UC (1994) High levels of a retinoic acid-generating dehydrogenase in the meso-telencephalic dopamine system. Proc Natl Acad Sci USA 91, 7772–7776.CrossRefGoogle ScholarPubMed
Maden, M, Gale, E & Zile, M (1998) The role of vitamin A in the development of the central nervous system. J Nutr 128, 471S–475S.CrossRefGoogle ScholarPubMed
Malik, MA, Blusztajn, JK & Greenwood, CE (2000) Nutrients as trophic factors in neurons and the central nervous system: Role of retinoic acid. J Nutr Biochem 11, 2–13.CrossRefGoogle ScholarPubMed
Mangelsdorf, DJ, Borgmeyer, U & Heyman, RA, et al. (1992) Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev 6, 329–344.CrossRefGoogle ScholarPubMed
Martinez de Arrieta, C, Morte, B, Coloma, A & Bernal, J (1999) The human RC3 gene homolog, NRGN contains a thyroid hormone-responsive element located in the first intron. Endocrinology 140, 335–343.CrossRefGoogle ScholarPubMed
Misner, DL, Jacobs, S & Shimizu, Y, et al. (2001) Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity. Proc Natl Acad Sci USA 98, 11714–11719.CrossRefGoogle ScholarPubMed
Morte, B, Iñiguez, MA, Lorenzo, PI & Bernal, J (1997) Thyroid hormone-regulated expression of RC3/neurogranin in the immortalized hypothalamic cell line GT1-7. J Neurochem 69, 902–909.CrossRefGoogle ScholarPubMed
Murray, MB, Zilz, ND, McCreary, NL, MacDonald, MJ & Towle, HC (1988) Isolation and characterization of rat cDNA clones for two distinct thyroid hormone receptors. J Biol Chem 263, 12770–12777.CrossRefGoogle ScholarPubMed
Okamura, K, Taurog, A & Distefano, JJ (1981) Elevated serum levels of T3 without metabolic effect in nutritionally deficient rats, attributable to reduced cellular uptake of T3. Endocrinology 109, 673–675.CrossRefGoogle ScholarPubMed
Pailler-Rodde, I, Garcin, H, Higueret, P & Begueret, J (1991) c-erb-A mRNA content and triiodothyronine nuclear receptor binding capacity in rat liver according to vitamin A status. FEBS Lett 289, 33–36.CrossRefGoogle ScholarPubMed
Pak, JH, Huang, FL, Li, J, et al. (2000) Involvement of neurogranin in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: a study with knockout mice. Proc Natl Acad Sci USA 97, 11232–11237.CrossRefGoogle ScholarPubMed
Pallet, V, Audouin-Chevallier, I, Verret, C, Garcin, H & Higueret, P (1994) Retinoic acid differentially modulates triiodothyronine and retinoic acid receptors in rat liver according to thyroid status. Eur J Endocrinol 131, 377–384.CrossRefGoogle ScholarPubMed
Sabath, DE, Broome, HE & Prystowsky, MB (1990) Glyceraldehyde-3-phosphate dehydrogenase mRNA is a major interleukin 2-induced transcript in a cloned T-helper lymphocyte. Gene 91, 185–191.CrossRefGoogle Scholar
Savouré, N, Nio, C, Maudet, M & Nicol, M (1996) Liver transglutaminases and vitamin-A deficiency in hairless mice. Ann Nutr Metab 40, 52–60.Google ScholarPubMed
Schräder, M & Carlberg, C (1994) Thyroid hormone and retinoic acid receptors form heterodimers with retinoid X receptors on direct repeats, palindromes, and inverted palindromes. DNA Cell Biol 13, 333–341.CrossRefGoogle ScholarPubMed
Sporn, MB, Roberts, AB & Goodman, DS (1994) In The Retinoids, Biology, Chemistry and Medicine. 2nd ed., New York, NY: Raven Press.Google Scholar
Sterling, P & Eyer, J (1988) Allostasis: A new paradigm to explain arousal pathology. In Handbook of Life Stress, Cognition and Health. pp 629–649. [Fisher, S and Reason, J, editors]. Chichester, UK: John Wiley.Google Scholar
Verma, AK, Shoemaker, A, Simsiman, R, Denning, M & Zachman, R (1992) Expression of retinoic acid nuclear receptors and tissue transglutaminase is altered in various tissues of rats fed with a vitamin A-deficient diet. J Nutr 122, 2144–2152.CrossRefGoogle ScholarPubMed
Watson, JB, Battenberg, EF, Wong, KK, Bloom, FE & Sutcliffe, J (1990) Subtractive cDNA cloning of RC3, a rodent cortex-enriched mRNA encoding a novel 78 residue protein. J Neurosci Res 26, 397–408.CrossRefGoogle ScholarPubMed
Yagamata, T, Momoi, T, Kumagai, H, Nishikawa, T, Yanagisawa, M & Momoi, M (1993) Distribution of retinoic acid receptor β proteins in rat brain: up-regulation by retinoic acid. Biomed Res 14, 183–190.CrossRefGoogle Scholar
Zelent, A, Krust, A, Petkovich, M, Kastner, P & Chambon, P (1989) Cloning of murine alpha and beta retinoic acid receptors and a novel receptor gamma predominantly expressed in skin. Nature 339, 714–717.CrossRefGoogle Scholar
Zetterström, RH, Lindqvist, E, Mata de Urquiza, A, et al. (1999) Role of retinoids in the CNS: differential expression of retinoid binding proteins and receptors and evidence for presence of retinoic acid. Eur J Neurosci 11, 407–416.CrossRefGoogle ScholarPubMed