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

ABSTRACT: 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.

SUBMITTER: Vennin C

PROVIDER: S-EPMC9655779 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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

Vennin Constance C Hewel Charlotte C Todorov Hristo H Wendelmuth Marlon M Radyushkin Konstantin K Heimbach André A Horenko Illia I Ayash Sarah S Müller Marianne B MB Schweiger Susann S Gerber Susanne S Lutz Beat B

Cells 20221027 21

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 ...[more]

PMID: 36359800

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Project description:BackgroundAnhedonia, or diminished interest or pleasure in rewarding activities, characterizes depression and reflects deficits in brain reward circuitries. Social stress induces anhedonia and increases risk of depression, although the effect of social stress on brain reward function is incompletely understood.MethodsThis study assessed the following: 1) brain reward function in rats (using the intracranial self-stimulation procedure) and protein levels of brain-derived neurotrophic factor and related signaling molecules in response to chronic social defeat, 2) brain reward function during social defeat and long-term treatment with the antidepressants fluoxetine (5 mg/kg/day) and desipramine (10 mg/kg/day), and 3) forced swim test behavior after social defeat and fluoxetine treatment.ResultsSocial defeat profoundly and persistently decreased brain reward function, reflecting an enduring anhedonic response, in susceptible rats, whereas resilient rats showed no long-term brain reward deficits. In the ventral tegmental area, social defeat, regardless of susceptibility or resilience, decreased brain-derived neurotrophic factor and increased phosphorylated AKT, whereas only susceptibility was associated with increased phosphorylated mammalian target of rapamycin. Fluoxetine and desipramine reversed lower, but not higher, stress-induced brain reward deficits in susceptible rats. Fluoxetine decreased immobility in the forced swim test, as did social defeat.ConclusionsThese results suggest that the differential persistent anhedonic response to psychosocial stress may be mediated by ventral tegmental area signaling molecules independent of brain-derived neurotrophic factor and indicate that greater stress-induced anhedonia is associated with resistance to antidepressant treatment. Consideration of these behavioral and neurobiological factors associated with resistance to stress and antidepressant action may promote the discovery of novel targets to treat stress-related mood disorders.

Dataset Information

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

Publications

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

Similar Datasets

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