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

doi:10.3390/cells11213405

Cited by 5 publications

(2 citation statements)

References 80 publications

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“…For instance, Venin et al 2022 and colleagues employed a modi ed social interaction test followed by single cell RNA-seq, revealing a subgroup of mice within the traditionally classi ed susceptible group (termed intermediate), which exhibited an active and dynamic non-neuronal molecular response associated with brain restoration and homeostasis, potentially contributing to stress resilience. This newly classi ed intermediate subgroup exhibited transcriptional overexpression of genes related to oligodendrogenesis, myelin differentiation glial cell activation in the dorsal hippocampus [22]. The potential involvement of oligodendrocytes, as highlighted also by our study, might suggest a more important pathway that has not been considered previously and which might require further investigation.…”

Section: Discussionmentioning

confidence: 48%

Characterization of transcriptional profiles associated with stress-induced neuronal activation in Arc-GFP mice

Gerber,

Butto,

Winter

et al. 2023

Preprint

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Chronic stress has become a predominant factor associated with a variety of psychiatric disorders, such as depression and anxiety, in both humans and animal models. Although multiple studies have looked at transcriptional changes after social defeat stress, these studies mostly focus on bulk tissues, which might dilute important molecular signatures of social interaction in activated cells. In this study, we employed the Arc-GFP mouse model in conjunction with chronic social defeat (CSD) to selectively isolate activated nuclei (AN) populations in the ventral hippocampus (vHIP) and prefrontal cortex (PFC) of resilient and susceptible animals. Nuclear RNA-seq of susceptible vs. resilient populations revealed distinct transcriptional profiles linked predominantly with neuronal and synaptic regulation mechanisms. In the vHIP, susceptible AN exhibited increased expression of genes related to cytoskeleton and synaptic organization while resilient AN showed upregulation of cell adhesion genes and differential expression of major glutamatergic subunits. In the PFC, susceptible mice exhibited upregulation of synaptotagmins, and immediate early genes (IEGs), suggesting a potentially over-amplified neuronal activity state. Our findings provide a novel view of stress-exposed neuronal activation and the molecular response mechanisms in stress-susceptible versus resilient animals, which may have important implications for understanding mental resilience.

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Section: Discussionmentioning

confidence: 48%

Characterization of transcriptional profiles associated with stress-induced neuronal activation in Arc-GFP mice

Gerber,

Butto,

Winter

et al. 2023

Preprint

Self Cite

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“…3A ). In the brain of male mice after CSDS, it has been demonstrated that the most reproducible transcriptome changes are the expression of hemoglobin genes [ 38 , 39 ], which is believed to provide neuroprotection in response to oxidative stress [ 40 ]. Intriguingly, the expression of hemoglobin genes Hba‐a1 , Hba‐a2 , Hbb‐bs , and Hbb‐bt was detected in the kidney of male C57 BL/6 mice and showed a trend of up‐regulation after CSDS although it failed to reach statistical difference (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine partially alleviates inflammation in the kidney of socially stressed male C57 BL/6 mice

Jin

et al. 2023

FEBS Open Bio

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Stress‐related illnesses are linked to the onset and progression of renal diseases and depressive disorders. To investigate stress‐induced changes in the renal transcriptome associated with the development of depressive behaviors, we generated here a chronic social defeat stress (CSDS) model of C57 BL/6 male mice and then performed RNA sequencing of the kidneys to obtain an inflammation‐related transcriptome. Administration of the antidepressant drug fluoxetine (10 mg·kg−1·day−1) during CSDS induction could partially alleviate renal inflammation and reverse CSDS‐induced depression‐like behaviors. Moreover, fluoxetine also modulated gene expression of stress‐related hormone receptors, including prolactin and melanin‐concentrating hormone. These results suggest that CSDS can induce gene expression changes associated with inflammation in the kidney of C57 BL/6 male mice, and this inflammation can be treated effectively by fluoxetine.

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Amitriptyline and cholecalciferol amend hippocampal histological structure and myelination during stress in Wistar rats via regulating miR200/BMP4/Olig‐2 signaling

Roushdy,

Labib,

Abdelrahim

et al. 2024

Cell Biology International

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Chronic stress is a universal condition commonly associated with many psychiatric diseases. An extensive body of evidence discussed hippocampal affection upon chronic stress exposure, however, the underlying molecular pathways still need to be identified. We investigated the impact of chronic stress on miR200/BMP/Olig‐2 signaling and hippocampal myelination. We also compared the effects of chronic administration of amitriptyline and cholecalciferol on chronically stressed hippocampi. Both amitriptyline and cholecalciferol significantly decreased serum cortisol levels, reduced immobility time in the forced swim test, increased the number of crossed squares in open field test, decreased the hippocampal expression of bone morphogenetic protein 4 (BMP4) and its messenger RNA (mRNA) levels, reduced miR200 expression as compared to untreated chronically stressed rats. Also, both drugs amended the hippocampal neuronal damage, enhanced the surviving cell count, and increased the pyramidal layer thickness of Cornu Ammonis subregion 1 (CA1) and granule cell layer of the dentate gyrus. Cholecalciferol was more effective in increasing the area percentage of myelin basic protein (MBP) and Olig‐2 positive cells count in hippocampi of chronic stress‐exposed rats than amitriptyline, thus enhancing myelination. We also found a negative correlation between the expression of BMP4, its mRNA, miR200, and the immunoexpression of MBP and Olig‐2 proteins. This work underscores the amelioration of the stress‐induced behavioral changes, inhibition of miR200/BMP4 signaling, and enhancement of hippocampal myelination following chronic administration of either amitriptyline or cholecalciferol, though cholecalciferol seemed more effective in brain remyelination.

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

Cited by 5 publications

References 80 publications

Characterization of transcriptional profiles associated with stress-induced neuronal activation in Arc-GFP mice

Characterization of transcriptional profiles associated with stress-induced neuronal activation in Arc-GFP mice

Fluoxetine partially alleviates inflammation in the kidney of socially stressed male C57 BL/6 mice

Amitriptyline and cholecalciferol amend hippocampal histological structure and myelination during stress in Wistar rats via regulating miR200/BMP4/Olig‐2 signaling

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