Retinoid hyposignaling contributes to aging-related decline in hippocampal function in short-term/working memory organization and long-term declarative memory encoding in mice
| Autor: | Frédérique Mingaud, Véronique Pallet, Betty Niedergang, Robert Jaffard, Wojciech Krezel, Paul Higueret, Nicole Etchamendy, Aline Marighetto, Marta Wietrzych, Nicole Mons, Cécile Mormède |
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| Přispěvatelé: | Centre de neurosciences intégratives et cognitives (CNIC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Peney, Maité, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Centre Neurosciences Integratives et Cognitives, Universite´ Bordeaux 1, Centre National de la Recherche Scientifique, Unite´ Mixte de Recherche 5228, 33405 Talence, France, Unite´ Nutrition et Neurosciences, Universite´ Bordeaux 1-2, 33405 Talence, France, Centre Neurosciences Inte´gratives et Cognitives, Universite´ Bordeaux 1, Centre National de la Recherche Scientifique, Unite´ Mixte de Recherche 5228, 33405 Talence, France, Centre Neurosciences Inte´gratives et Cognitives, Universite´ Bordeaux 1, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5228, 33405 Talence, France, Centre Neurosciences Inte´gratives et Cognitives, Universite´ Bordeaux 1, Centre National de la Recherche Scientifique, Unit Mixte de Recherche 5228, 33405 Talence, France, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Aging
Time Factors MESH: Hippocampus Receptors Retinoic Acid [SDV]Life Sciences [q-bio] Retinoic acid RARΒ/RXRΓ Hippocampal formation [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Hippocampus MESH: Mice Knockout Procedural memory chemistry.chemical_compound Mice 0302 clinical medicine GAP-43 Protein MESH: GAP-43 Protein MESH: Behavior Animal MESH: Aging MESH: Animals Retinoid Vitamin A ComputingMilieux_MISCELLANEOUS MESH: Vitamin A Mice Knockout INTERFERENCE 0303 health sciences Behavior Animal General Neuroscience FOS Long-term potentiation Articles MESH: Memory Disorders PROACTIVE Memory Short-Term MESH: Retinoid X Receptors GAP43 Psychology medicine.drug_class Tretinoin MESH: Memory Short-Term 03 medical and health sciences Retinoids Keratolytic Agents MESH: Keratolytic Agents MESH: Mice Inbred C57BL medicine Animals MESH: Retinoids Maze Learning MESH: Mice 030304 developmental biology KNOCK-OUT MESH: Receptors Retinoic Acid Memory Disorders Radial arm maze NUTRITIONAL SUPPLEMENTATION MESH: Tretinoin Working memory MESH: Maze Learning MESH: Time Factors [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Retinoid X receptor gamma Mice Inbred C57BL Retinoid X Receptors chemistry RADIAL ARM MAZE Neuroscience 030217 neurology & neurosurgery NUCLEAR RECEPTORS |
| Zdroj: | Journal of Neuroscience Journal of Neuroscience, Society for Neuroscience, 2008, 28 (1), pp.279-91. ⟨10.1523/JNEUROSCI.4065-07.2008⟩ Journal of Neuroscience, 2008, 28 (1), pp.279-91. ⟨10.1523/JNEUROSCI.4065-07.2008⟩ Journal of Neuroscience, Society for Neuroscience, 2008, 28 (1), pp.279-291. ⟨10.1523/JNEUROSCI.4065-07.2008⟩ |
| ISSN: | 0270-6474 1529-2401 |
| Popis: | 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 γ, 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. |
| Databáze: | OpenAIRE |
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