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USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder

USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder

Authors :
Hôpitaux de Paris
Cheron, Julian
Beccari, Leonardo
Hagué, Perrine
Icick, Romain
Despontin, Chloé
Carusone, Teresa
Defrance, Matthieu
Bhogaraju, Sagar
Martin-Garcia, Elena
Capellan, Roberto
Maldonado, Rafael
Vorspan, Florence
Bonnefont, Jérôme
de Kerchove d'Exaerde, Alban
Hôpitaux de Paris
Cheron, Julian
Beccari, Leonardo
Hagué, Perrine
Icick, Romain
Despontin, Chloé
Carusone, Teresa
Defrance, Matthieu
Bhogaraju, Sagar
Martin-Garcia, Elena
Capellan, Roberto
Maldonado, Rafael
Vorspan, Florence
Bonnefont, Jérôme
de Kerchove d'Exaerde, Alban
Publication Year :
2023

Abstract

The risk of developing drug addiction is strongly influenced by the epigenetic landscape and chromatin remodeling. While histone modifications such as methylation and acetylation have been studied in the ventral tegmental area and nucleus accumbens (NAc), the role of H2A monoubiquitination remains unknown. Our investigations, initially focused on the scaffold protein melanoma-associated antigen D1 (Maged1), reveal that H2A monoubiquitination in the paraventricular thalamus (PVT) significantly contributes to cocaine-adaptive behaviors and transcriptional repression induced by cocaine. Chronic cocaine use increases H2A monoubiquitination, regulated by Maged1 and its partner USP7. Accordingly, Maged1 specific inactivation in thalamic Vglut2 neurons, or USP7 inhibition, blocks cocaine-evoked H2A monoubiquitination and cocaine locomotor sensitization. Additionally, genetic variations in MAGED1 and USP7 are linked to altered susceptibility to cocaine addiction and cocaine-associated symptoms in humans. These findings unveil an epigenetic modification in a non-canonical reward pathway of the brain and a potent marker of epigenetic risk factors for drug addiction in humans.

Details

Database :
OAIster
Publication Type :
Electronic Resource
Accession number :
edsoai.on1442726505
Document Type :
Electronic Resource