Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator

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

doi:10.15252/emmm.201708587

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Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator

Journal article

Open access

Peer reviewed

Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator

Snehajyoti Chatterjee, Raphaelle Cassel, Anne Schneider-Anthony, Karine Merienne, Brigitte Cosquer, Laura Tzeplaeff, Sarmistha Halder Sinha, Manoj Kumar, Piyush Chaturbedy, Muthusamy Eswaramoorthy, …

EMBO molecular medicine, Vol.10(11), pp.e8587-n/a

11/2018

DOI: 10.15252/emmm.201708587

PMCID: PMC6220301

PMID: 30275019

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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 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.

Acetylation - drug effects

Animals

Disease Models, Animal

Enzyme Activators - pharmacology

Epigenesis, Genetic - drug effects

Hippocampus - drug effects

Hippocampus - metabolism

Histones - metabolism

Inflammation - pathology

Memory - drug effects

Mice, Inbred C57BL

Mice, Transgenic

Neuronal Plasticity - drug effects

p300-CBP Transcription Factors - metabolism

Tauopathies - genetics

Tauopathies - physiopathology

Transcriptome - drug effects

Transcriptome - genetics

Transgenes

Details

Title: Subtitle: Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator
Creators: Snehajyoti Chatterjee - Laboratoire de Neurosciences Cognitives et Adaptatives
Raphaelle Cassel - Laboratoire de Neurosciences Cognitives et Adaptatives
Anne Schneider-Anthony - Laboratoire de Neurosciences Cognitives et Adaptatives
Karine Merienne - Laboratoire de Neurosciences Cognitives et Adaptatives
Brigitte Cosquer - Laboratoire de Neurosciences Cognitives et Adaptatives
Laura Tzeplaeff - Laboratoire de Neurosciences Cognitives et Adaptatives
Sarmistha Halder Sinha - Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India
Manoj Kumar - Jawaharlal Nehru Centre for Advanced Scientific Research
Piyush Chaturbedy - Jawaharlal Nehru Centre for Advanced Scientific Research
Muthusamy Eswaramoorthy - Jawaharlal Nehru Centre for Advanced Scientific Research
Stéphanie Le Gras - University of Strasbourg
Céline Keime - University of Strasbourg
Olivier Bousiges - Laboratoire de Neurosciences Cognitives et Adaptatives
Patrick Dutar - Délégation Paris 5
Petnoi Petsophonsakul - Research Centre on Animal Cognition
Claire Rampon - Research Centre on Animal Cognition
Jean-Christophe Cassel - Laboratoire de Neurosciences Cognitives et Adaptatives
Luc Buée - Lille University of Science and Technology
David Blum - Lille University of Science and Technology
Tapas K Kundu - Jawaharlal Nehru Centre for Advanced Scientific Research
Anne-Laurence Boutillier - Laboratoire de Neurosciences Cognitives et Adaptatives
Resource Type: Journal article
Publication Details: EMBO molecular medicine, Vol.10(11), pp.e8587-n/a
DOI: 10.15252/emmm.201708587
PMID: 30275019
PMCID: PMC6220301
NLM abbreviation: EMBO Mol Med
ISSN: 1757-4676
eISSN: 1757-4684
Grant note: DOI: 10.13039/501100001665, name: Agence Nationale de la Recherche, award: ANR‐12‐MALZ‐0002‐01, ANR‐10‐INBS‐0009; DOI: 10.13039/501100002915, name: Fondation pour la Recherche Médicale; DOI: 10.13039/501100004794, name: Centre National de la Recherche Scientifique; DOI: 10.13039/501100003768, name: Université de Strasbourg; DOI: 10.13039/501100003750, name: Association France Alzheimer; DOI: 10.13039/501100001677, name: Institut National de la Santé et de la Recherche Médicale; DOI: 10.13039/501100007856, name: Université Lille 1 - Sciences et Technologies
Language: English
Date published: 11/2018
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984303745302771

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