Cargando…

A Resilience Related Glial-Neurovascular Network Is Transcriptionally Activated after Chronic Social Defeat in Male Mice

Upon chronic stress, a fraction of individuals shows stress resilience, which can prevent long-term mental dysfunction. The underlying molecular mechanisms are complex and have not yet been fully understood. In this study, we performed a data-driven behavioural stratification together with single-ce...

Descripción completa

Detalles Bibliográficos
Autores principales: Vennin, Constance, Hewel, Charlotte, Todorov, Hristo, Wendelmuth, Marlon, Radyushkin, Konstantin, Heimbach, André, Horenko, Illia, Ayash, Sarah, Müller, Marianne B., Schweiger, Susann, Gerber, Susanne, Lutz, Beat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655779/
https://www.ncbi.nlm.nih.gov/pubmed/36359800
http://dx.doi.org/10.3390/cells11213405
_version_ 1784829270235807744
author Vennin, Constance
Hewel, Charlotte
Todorov, Hristo
Wendelmuth, Marlon
Radyushkin, Konstantin
Heimbach, André
Horenko, Illia
Ayash, Sarah
Müller, Marianne B.
Schweiger, Susann
Gerber, Susanne
Lutz, Beat
author_facet Vennin, Constance
Hewel, Charlotte
Todorov, Hristo
Wendelmuth, Marlon
Radyushkin, Konstantin
Heimbach, André
Horenko, Illia
Ayash, Sarah
Müller, Marianne B.
Schweiger, Susann
Gerber, Susanne
Lutz, Beat
author_sort Vennin, Constance
collection PubMed
description Upon chronic stress, a fraction of individuals shows stress resilience, which can prevent long-term mental dysfunction. The underlying molecular mechanisms are complex and have not yet been fully understood. In this study, we performed a data-driven behavioural stratification together with single-cell transcriptomics of the hippocampus in a mouse model of chronic social defeat stress. Our work revealed that in a sub-group exhibiting molecular responses upon chronic stress, the dorsal hippocampus is particularly involved in neuroimmune responses, angiogenesis, myelination, and neurogenesis, thereby enabling brain restoration and homeostasis after chronic stress. Based on these molecular insights, we applied rapamycin after the stress as a proof-of-concept pharmacological intervention and were able to substantially increase stress resilience. Our findings serve as a data resource and can open new avenues for further understanding of molecular processes underlying stress response and for targeted interventions supporting resilience.
format Online
Article
Text
id pubmed-9655779
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96557792022-11-15 A Resilience Related Glial-Neurovascular Network Is Transcriptionally Activated after Chronic Social Defeat in Male Mice Vennin, Constance Hewel, Charlotte Todorov, Hristo Wendelmuth, Marlon Radyushkin, Konstantin Heimbach, André Horenko, Illia Ayash, Sarah Müller, Marianne B. Schweiger, Susann Gerber, Susanne Lutz, Beat Cells Article Upon chronic stress, a fraction of individuals shows stress resilience, which can prevent long-term mental dysfunction. The underlying molecular mechanisms are complex and have not yet been fully understood. In this study, we performed a data-driven behavioural stratification together with single-cell transcriptomics of the hippocampus in a mouse model of chronic social defeat stress. Our work revealed that in a sub-group exhibiting molecular responses upon chronic stress, the dorsal hippocampus is particularly involved in neuroimmune responses, angiogenesis, myelination, and neurogenesis, thereby enabling brain restoration and homeostasis after chronic stress. Based on these molecular insights, we applied rapamycin after the stress as a proof-of-concept pharmacological intervention and were able to substantially increase stress resilience. Our findings serve as a data resource and can open new avenues for further understanding of molecular processes underlying stress response and for targeted interventions supporting resilience. MDPI 2022-10-27 /pmc/articles/PMC9655779/ /pubmed/36359800 http://dx.doi.org/10.3390/cells11213405 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vennin, Constance
Hewel, Charlotte
Todorov, Hristo
Wendelmuth, Marlon
Radyushkin, Konstantin
Heimbach, André
Horenko, Illia
Ayash, Sarah
Müller, Marianne B.
Schweiger, Susann
Gerber, Susanne
Lutz, Beat
A Resilience Related Glial-Neurovascular Network Is Transcriptionally Activated after Chronic Social Defeat in Male Mice
title A Resilience Related Glial-Neurovascular Network Is Transcriptionally Activated after Chronic Social Defeat in Male Mice
title_full A Resilience Related Glial-Neurovascular Network Is Transcriptionally Activated after Chronic Social Defeat in Male Mice
title_fullStr A Resilience Related Glial-Neurovascular Network Is Transcriptionally Activated after Chronic Social Defeat in Male Mice
title_full_unstemmed A Resilience Related Glial-Neurovascular Network Is Transcriptionally Activated after Chronic Social Defeat in Male Mice
title_short A Resilience Related Glial-Neurovascular Network Is Transcriptionally Activated after Chronic Social Defeat in Male Mice
title_sort resilience related glial-neurovascular network is transcriptionally activated after chronic social defeat in male mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655779/
https://www.ncbi.nlm.nih.gov/pubmed/36359800
http://dx.doi.org/10.3390/cells11213405
work_keys_str_mv AT venninconstance aresiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT hewelcharlotte aresiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT todorovhristo aresiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT wendelmuthmarlon aresiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT radyushkinkonstantin aresiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT heimbachandre aresiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT horenkoillia aresiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT ayashsarah aresiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT mullermarianneb aresiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT schweigersusann aresiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT gerbersusanne aresiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT lutzbeat aresiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT venninconstance resiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT hewelcharlotte resiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT todorovhristo resiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT wendelmuthmarlon resiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT radyushkinkonstantin resiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT heimbachandre resiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT horenkoillia resiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT ayashsarah resiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT mullermarianneb resiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT schweigersusann resiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT gerbersusanne resiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice
AT lutzbeat resiliencerelatedglialneurovascularnetworkistranscriptionallyactivatedafterchronicsocialdefeatinmalemice