QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 2, 2008, 28(1):279-291; doi:10.1523/JNEUROSCI.4065-07.2008

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Mingaud, F. Articles by Marighetto, A. Search for Related Content PubMed PubMed Citation Articles by Mingaud, F. Articles by Marighetto, A.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Retinoid Hyposignaling Contributes to Aging-Related Decline in Hippocampal Function in Short-Term/Working Memory Organization and Long-Term Declarative Memory Encoding in Mice

Frédérique Mingaud,^1,2 Cécile Mormede,^1,2 Nicole Etchamendy,¹ Nicole Mons,¹ Betty Niedergang,¹ Marta Wietrzych,³ Véronique Pallet,² Robert Jaffard,¹ Wojciech Krezel,³ Paul Higueret,² and Aline Marighetto¹

¹Centre Neurosciences Intégratives et Cognitives, Université Bordeaux 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5228, 33405 Talence, France, ²Unité Nutrition et Neurosciences, Université Bordeaux 1-2, 33405 Talence, France, and ³Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France

Correspondence should be addressed to Dr. A. Marighetto, Centre Neurosciences Intégratives et Cognitives, Université Bordeaux 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5228, 33405 Talence, France. Email: a.marighetto{at}cnic.u-bordeaux1.fr

An increasing body of evidence indicates that the vitamin A metabolite retinoic acid (RA) plays a role in adult brain plasticity by activating gene transcription through nuclear receptors. Our previous studies in mice have shown that a moderate downregulation of retinoid-mediated transcription contributed to aging-related deficits in hippocampal long-term potentiation and long-term declarative memory (LTDM). Here, knock-out, pharmacological, and nutritional approaches were used in a series of radial-arm maze experiments with mice to further assess the hypothesis that retinoid-mediated nuclear events are causally involved in preferential degradation of hippocampal function in aging. Molecular and behavioral findings confirmed our hypothesis. First, a lifelong vitamin A supplementation, like short-term RA administration, was shown to counteract the aging-related hippocampal (but not striatal) hypoexpression of a plasticity-related retinoid target-gene, GAP43 (reverse transcription-PCR analyses, experiment 1), as well as short-term/working memory (STWM) deterioration seen particularly in organization demanding trials (STWM task, experiment 2). Second, using a two-stage paradigm of LTDM, we demonstrated that the vitamin A supplementation normalized memory encoding-induced recruitment of (hippocampo-prefrontal) declarative memory circuits, without affecting (striatal) procedural memory system activity in aged mice (Fos neuroimaging, experiment 3A) and alleviated their LTDM impairment (experiment 3B). Finally, we showed that (knock-out, experiment 4) RA receptor β and retinoid X receptor , known to be involved in STWM (Wietrzych et al., 2005), are also required for LTDM. Hence, aging-related retinoid signaling hypoexpression disrupts hippocampal cellular properties critically required for STWM organization and LTDM formation, and nutritional vitamin A supplementation represents a preventive strategy. These findings are discussed within current neurobiological perspectives questioning the historical consensus on STWM and LTDM system partition.

Key words: nutritional supplementation; RARβ/RXR; nuclear receptors; knock-out; GAP43; Fos; proactive; interference; radial arm maze

---

Received Feb. 27, 2007; revised Oct. 23, 2007; accepted Nov. 15, 2007.

Correspondence should be addressed to Dr. A. Marighetto, Centre Neurosciences Intégratives et Cognitives, Université Bordeaux 1, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5228, 33405 Talence, France. Email: a.marighetto{at}cnic.u-bordeaux1.fr

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help