Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator
Abstract Chromatin acetylation, a critical regulator of synaptic plasticity and memory processes, is thought to be altered in neurodegenerative diseases. Here, we demonstrate that spatial memory and plasticity (LTD, dendritic spine formation) deficits can be restored in a mouse model of tauopathy fo...
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Format: | Article |
Language: | English |
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Wiley
2018-11-01
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Series: | EMBO Molecular Medicine |
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Online Access: | https://doi.org/10.15252/emmm.201708587 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Snehajyoti Chatterjee Raphaelle Cassel Anne Schneider‐Anthony Karine Merienne Brigitte Cosquer Laura Tzeplaeff Sarmistha Halder Sinha Manoj Kumar Piyush Chaturbedy Muthusamy Eswaramoorthy Stéphanie Le Gras Céline Keime Olivier Bousiges Patrick Dutar Petnoi Petsophonsakul Claire Rampon Jean‐Christophe Cassel Luc Buée David Blum Tapas K Kundu Anne‐Laurence Boutillier |
spellingShingle |
Snehajyoti Chatterjee Raphaelle Cassel Anne Schneider‐Anthony Karine Merienne Brigitte Cosquer Laura Tzeplaeff Sarmistha Halder Sinha Manoj Kumar Piyush Chaturbedy Muthusamy Eswaramoorthy Stéphanie Le Gras Céline Keime Olivier Bousiges Patrick Dutar Petnoi Petsophonsakul Claire Rampon Jean‐Christophe Cassel Luc Buée David Blum Tapas K Kundu Anne‐Laurence Boutillier Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator EMBO Molecular Medicine acetylation Alzheimer's disease CREB‐binding protein learning transcription |
author_facet |
Snehajyoti Chatterjee Raphaelle Cassel Anne Schneider‐Anthony Karine Merienne Brigitte Cosquer Laura Tzeplaeff Sarmistha Halder Sinha Manoj Kumar Piyush Chaturbedy Muthusamy Eswaramoorthy Stéphanie Le Gras Céline Keime Olivier Bousiges Patrick Dutar Petnoi Petsophonsakul Claire Rampon Jean‐Christophe Cassel Luc Buée David Blum Tapas K Kundu Anne‐Laurence Boutillier |
author_sort |
Snehajyoti Chatterjee |
title |
Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator |
title_short |
Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator |
title_full |
Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator |
title_fullStr |
Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator |
title_full_unstemmed |
Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator |
title_sort |
reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator |
publisher |
Wiley |
series |
EMBO Molecular Medicine |
issn |
1757-4676 1757-4684 |
publishDate |
2018-11-01 |
description |
Abstract Chromatin acetylation, a critical regulator of synaptic plasticity and memory processes, is thought to be altered in neurodegenerative diseases. Here, we demonstrate that spatial memory and plasticity (LTD, dendritic spine formation) deficits can be restored in a mouse model of tauopathy following treatment with CSP‐TTK21, a small‐molecule activator of CBP/p300 histone acetyltransferases (HAT). At the transcriptional level, CSP‐TTK21 re‐established half of the hippocampal transcriptome in learning mice, likely through increased expression of neuronal activity genes and memory enhancers. At the epigenomic level, the hippocampus of tauopathic mice showed a significant decrease in H2B but not H3K27 acetylation levels, both marks co‐localizing at TSS and CBP enhancers. Importantly, CSP‐TTK21 treatment increased H2B acetylation levels at decreased peaks, CBP enhancers, and TSS, including genes associated with plasticity and neuronal functions, overall providing a 95% rescue of the H2B acetylome in tauopathic mice. This study is the first to provide in vivo proof‐of‐concept evidence that CBP/p300 HAT activation efficiently reverses epigenetic, transcriptional, synaptic plasticity, and behavioral deficits associated with Alzheimer's disease lesions in mice. |
topic |
acetylation Alzheimer's disease CREB‐binding protein learning transcription |
url |
https://doi.org/10.15252/emmm.201708587 |
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doaj-3e3bcfa696b14836b0aa51926f42e2db2021-08-02T12:19:01ZengWileyEMBO Molecular Medicine1757-46761757-46842018-11-011011n/an/a10.15252/emmm.201708587Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activatorSnehajyoti Chatterjee0Raphaelle Cassel1Anne Schneider‐Anthony2Karine Merienne3Brigitte Cosquer4Laura Tzeplaeff5Sarmistha Halder Sinha6Manoj Kumar7Piyush Chaturbedy8Muthusamy Eswaramoorthy9Stéphanie Le Gras10Céline Keime11Olivier Bousiges12Patrick Dutar13Petnoi Petsophonsakul14Claire Rampon15Jean‐Christophe Cassel16Luc Buée17David Blum18Tapas K Kundu19Anne‐Laurence Boutillier20Laboratoire de Neuroscience Cognitives et Adaptatives (LNCA) Université de Strasbourg Strasbourg FranceLaboratoire de Neuroscience Cognitives et Adaptatives (LNCA) Université de Strasbourg Strasbourg FranceLaboratoire de Neuroscience Cognitives et Adaptatives (LNCA) Université de Strasbourg Strasbourg FranceLaboratoire de Neuroscience Cognitives et Adaptatives (LNCA) Université de Strasbourg Strasbourg FranceLaboratoire de Neuroscience Cognitives et Adaptatives (LNCA) Université de Strasbourg Strasbourg FranceLaboratoire de Neuroscience Cognitives et Adaptatives (LNCA) Université de Strasbourg Strasbourg FranceTranscription and Disease Laboratory Molecular Biology and Genetics Unit Jawaharlal Nehru Centre for Advanced Scientific Research Bangalore IndiaTranscription and Disease Laboratory Molecular Biology and Genetics Unit Jawaharlal Nehru Centre for Advanced Scientific Research Bangalore IndiaChemistry and Physics of Materials Unit Jawaharlal Nehru Centre for Advanced Scientific Research Bangalore IndiaChemistry and Physics of Materials Unit Jawaharlal Nehru Centre for Advanced Scientific Research Bangalore IndiaCNRS Inserm UMR 7104 Microarray and Sequencing Platform Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) Université de Strasbourg Illkirch FranceCNRS Inserm UMR 7104 Microarray and Sequencing Platform Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) Université de Strasbourg Illkirch FranceLaboratoire de Neuroscience Cognitives et Adaptatives (LNCA) Université de Strasbourg Strasbourg FranceCentre de Psychiatrie et Neurosciences INSERM UMRS894 Université Paris Descartes, Sorbonne Paris Cité Paris FranceCentre de Recherches sur la Cognition Animale Centre de Biologie Intégrative CNRS UPS Université de Toulouse Toulouse FranceCentre de Recherches sur la Cognition Animale Centre de Biologie Intégrative CNRS UPS Université de Toulouse Toulouse FranceLaboratoire de Neuroscience Cognitives et Adaptatives (LNCA) Université de Strasbourg Strasbourg FranceInserm CHU‐Lille UMR‐S 1172, Alzheimer & Tauopathies Université de Lille Lille FranceInserm CHU‐Lille UMR‐S 1172, Alzheimer & Tauopathies Université de Lille Lille FranceTranscription and Disease Laboratory Molecular Biology and Genetics Unit Jawaharlal Nehru Centre for Advanced Scientific Research Bangalore IndiaLaboratoire de Neuroscience Cognitives et Adaptatives (LNCA) Université de Strasbourg Strasbourg FranceAbstract Chromatin acetylation, a critical regulator of synaptic plasticity and memory processes, is thought to be altered in neurodegenerative diseases. Here, we demonstrate that spatial memory and plasticity (LTD, dendritic spine formation) deficits can be restored in a mouse model of tauopathy following treatment with CSP‐TTK21, a small‐molecule activator of CBP/p300 histone acetyltransferases (HAT). At the transcriptional level, CSP‐TTK21 re‐established half of the hippocampal transcriptome in learning mice, likely through increased expression of neuronal activity genes and memory enhancers. At the epigenomic level, the hippocampus of tauopathic mice showed a significant decrease in H2B but not H3K27 acetylation levels, both marks co‐localizing at TSS and CBP enhancers. Importantly, CSP‐TTK21 treatment increased H2B acetylation levels at decreased peaks, CBP enhancers, and TSS, including genes associated with plasticity and neuronal functions, overall providing a 95% rescue of the H2B acetylome in tauopathic mice. This study is the first to provide in vivo proof‐of‐concept evidence that CBP/p300 HAT activation efficiently reverses epigenetic, transcriptional, synaptic plasticity, and behavioral deficits associated with Alzheimer's disease lesions in mice.https://doi.org/10.15252/emmm.201708587acetylationAlzheimer's diseaseCREB‐binding proteinlearningtranscription |