Chronic Treatment with a Promnesiant GABA-A 𝜶𝟓-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model
Decrease of GABAergic transmission has been proposed to improve memory functions. Indeed, inverse agonists selective for α5 GABA-A-benzodiazepine receptors (α5IA) have promnesiant activity. Interestingly, we have recently shown that α5IA can rescue cognitive deficits in Ts65Dn mice, a Down syndrome...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2011-01-01
|
| Series: | Advances in Pharmacological Sciences |
| Online Access: | http://dx.doi.org/10.1155/2011/153218 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849691497405874176 |
|---|---|
| author | J. Braudeau L. Dauphinot A. Duchon A. Loistron R. H. Dodd Y. Hérault B. Delatour M. C. Potier |
| author_facet | J. Braudeau L. Dauphinot A. Duchon A. Loistron R. H. Dodd Y. Hérault B. Delatour M. C. Potier |
| author_sort | J. Braudeau |
| collection | DOAJ |
| description | Decrease of GABAergic transmission has been proposed to improve memory functions. Indeed, inverse agonists selective for α5 GABA-A-benzodiazepine receptors (α5IA) have promnesiant activity. Interestingly, we have recently shown that α5IA can rescue cognitive deficits in Ts65Dn mice, a Down syndrome mouse model with altered GABAergic transmission. Here, we studied the impact of chronic treatment with α5IA on gene expression in the hippocampus of Ts65Dn and control euploid mice after being trained in the Morris water maze task. In euploid mice, chronic treatment with α5IA increased IEGs expression, particularly of c-Fos and Arc genes. In Ts65Dn mice, deficits of IEGs activation were completely rescued after treatment with α5IA. In addition, normalization of Sod1 overexpression in Ts65Dn mice after α5IA treatment was observed. IEG expression regulation after α5IA treatment following behavioral stimulation could be a contributing factor for both the general promnesiant activity of α5IA and its rescuing effect in Ts65Dn mice alongside signaling cascades that are critical for memory consolidation and cognition. |
| format | Article |
| id | doaj-art-e7d457cc58184dafa204b2ca4a157715 |
| institution | DOAJ |
| issn | 1687-6334 1687-6342 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advances in Pharmacological Sciences |
| spelling | doaj-art-e7d457cc58184dafa204b2ca4a1577152025-08-20T03:21:01ZengWileyAdvances in Pharmacological Sciences1687-63341687-63422011-01-01201110.1155/2011/153218153218Chronic Treatment with a Promnesiant GABA-A 𝜶𝟓-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse ModelJ. Braudeau0L. Dauphinot1A. Duchon2A. Loistron3R. H. Dodd4Y. Hérault5B. Delatour6M. C. Potier7Centre de Recherche de l'Institut du Cerveau et de Moelle Epinière, INSERM UMRS 975, CNRS UMR7225, UPMC, 75013 Paris, FranceCentre de Recherche de l'Institut du Cerveau et de Moelle Epinière, INSERM UMRS 975, CNRS UMR7225, UPMC, 75013 Paris, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM) U964/Centre National de Recherche Scientifique (CNRS) UMR 1704/Université de Strasbourg, 67404 Illkirch, FranceCentre de Recherche de l'Institut du Cerveau et de Moelle Epinière, INSERM UMRS 975, CNRS UMR7225, UPMC, 75013 Paris, FranceInstitut de Chimie des Substances Naturelles-CNRS UPR 2301, 91198 Gif-sur-Yvette, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM) U964/Centre National de Recherche Scientifique (CNRS) UMR 1704/Université de Strasbourg, 67404 Illkirch, FranceCentre de Recherche de l'Institut du Cerveau et de Moelle Epinière, INSERM UMRS 975, CNRS UMR7225, UPMC, 75013 Paris, FranceCentre de Recherche de l'Institut du Cerveau et de Moelle Epinière, INSERM UMRS 975, CNRS UMR7225, UPMC, 75013 Paris, FranceDecrease of GABAergic transmission has been proposed to improve memory functions. Indeed, inverse agonists selective for α5 GABA-A-benzodiazepine receptors (α5IA) have promnesiant activity. Interestingly, we have recently shown that α5IA can rescue cognitive deficits in Ts65Dn mice, a Down syndrome mouse model with altered GABAergic transmission. Here, we studied the impact of chronic treatment with α5IA on gene expression in the hippocampus of Ts65Dn and control euploid mice after being trained in the Morris water maze task. In euploid mice, chronic treatment with α5IA increased IEGs expression, particularly of c-Fos and Arc genes. In Ts65Dn mice, deficits of IEGs activation were completely rescued after treatment with α5IA. In addition, normalization of Sod1 overexpression in Ts65Dn mice after α5IA treatment was observed. IEG expression regulation after α5IA treatment following behavioral stimulation could be a contributing factor for both the general promnesiant activity of α5IA and its rescuing effect in Ts65Dn mice alongside signaling cascades that are critical for memory consolidation and cognition.http://dx.doi.org/10.1155/2011/153218 |
| spellingShingle | J. Braudeau L. Dauphinot A. Duchon A. Loistron R. H. Dodd Y. Hérault B. Delatour M. C. Potier Chronic Treatment with a Promnesiant GABA-A 𝜶𝟓-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model Advances in Pharmacological Sciences |
| title | Chronic Treatment with a Promnesiant GABA-A 𝜶𝟓-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model |
| title_full | Chronic Treatment with a Promnesiant GABA-A 𝜶𝟓-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model |
| title_fullStr | Chronic Treatment with a Promnesiant GABA-A 𝜶𝟓-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model |
| title_full_unstemmed | Chronic Treatment with a Promnesiant GABA-A 𝜶𝟓-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model |
| title_short | Chronic Treatment with a Promnesiant GABA-A 𝜶𝟓-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model |
| title_sort | chronic treatment with a promnesiant gaba a 𝜶𝟓 selective inverse agonist increases immediate early genes expression during memory processing in mice and rectifies their expression levels in a down syndrome mouse model |
| url | http://dx.doi.org/10.1155/2011/153218 |
| work_keys_str_mv | AT jbraudeau chronictreatmentwithapromnesiantgabaaα5selectiveinverseagonistincreasesimmediateearlygenesexpressionduringmemoryprocessinginmiceandrectifiestheirexpressionlevelsinadownsyndromemousemodel AT ldauphinot chronictreatmentwithapromnesiantgabaaα5selectiveinverseagonistincreasesimmediateearlygenesexpressionduringmemoryprocessinginmiceandrectifiestheirexpressionlevelsinadownsyndromemousemodel AT aduchon chronictreatmentwithapromnesiantgabaaα5selectiveinverseagonistincreasesimmediateearlygenesexpressionduringmemoryprocessinginmiceandrectifiestheirexpressionlevelsinadownsyndromemousemodel AT aloistron chronictreatmentwithapromnesiantgabaaα5selectiveinverseagonistincreasesimmediateearlygenesexpressionduringmemoryprocessinginmiceandrectifiestheirexpressionlevelsinadownsyndromemousemodel AT rhdodd chronictreatmentwithapromnesiantgabaaα5selectiveinverseagonistincreasesimmediateearlygenesexpressionduringmemoryprocessinginmiceandrectifiestheirexpressionlevelsinadownsyndromemousemodel AT yherault chronictreatmentwithapromnesiantgabaaα5selectiveinverseagonistincreasesimmediateearlygenesexpressionduringmemoryprocessinginmiceandrectifiestheirexpressionlevelsinadownsyndromemousemodel AT bdelatour chronictreatmentwithapromnesiantgabaaα5selectiveinverseagonistincreasesimmediateearlygenesexpressionduringmemoryprocessinginmiceandrectifiestheirexpressionlevelsinadownsyndromemousemodel AT mcpotier chronictreatmentwithapromnesiantgabaaα5selectiveinverseagonistincreasesimmediateearlygenesexpressionduringmemoryprocessinginmiceandrectifiestheirexpressionlevelsinadownsyndromemousemodel |