Published November 16, 2021
| Version v1
Publication
SWI/SNF chromatin remodeler complex within the reward pathway is required for behavioral adaptations to stress
Contributors
Others:
- Neurosciences Paris Seine (NPS) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
- Institut Pasteur [Paris]
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- This work was supported by a Sorbonne Université grant (Emergence), the Labex BioPsy, the Foundation for Medical Research (FRM Equipe grant DEQ20140329552), the INCA (TABAC grant to PF, JB and FT), and the Agence Nationale de la Recherche (ANR3053NEUR31438301, ANR-14-CE35-0029-01 and ANR-15-CE16-0017).
- ANR-14-CE35-0029,PsyCoStress,Glucocorticoids and Psychiatric Disorders: Mechanisms of Stress Induced Cognitive Deficits(2014)
- ANR-15-CE16-0017,GLAD,Rôle des heteromères formés par les récepteurs dopamine-glutamate et de signalisation dépendante du calcium nucléaire associée dans l'addiction(2015)
Description
Stress exposure is a cardinal risk factor for most psychiatric diseases. Preclinical and clinical studies point to changes in gene expression involving epigenetic modifications within mesocorticolimbic brain circuits. Brahma (BRM) and Brahma-Related-Gene-1 (BRG1) are ATPase subunits of the SWI/SNF complexes involved in chromatin remodeling, a process essential to enduring plastic changes in gene expression. Here, we show that repeated social defeat induces changes in BRG1 nuclear distribution. The inactivation of the Brg1/Smarca4 gene within dopamine-innervated regions or the constitutive inactivation of the Brm/Smarca2 gene leads to resilience to repeated social defeat and decreases the behavioral responses to cocaine without impacting midbrain dopamine neurons activity. Within striatal medium spiny neurons Brg1 gene inactivation reduces the expression of stress-and cocaine-induced immediate early genes, increases levels of heterochromatin and at a global scale decreases chromatin accessibility. Altogether these data demonstrate the pivotal function of SWI/SNF complexes in behavioral and transcriptional adaptations to salient environmental challenges.
Additional details
Identifiers
- URL
- https://hal.archives-ouvertes.fr/hal-03422965
- URN
- urn:oai:HAL:hal-03422965v1
Origin repository
- Origin repository
- UNICA