Transcriptome Alterations Caused by Social Defeat Stress of Various Durations in Mice and Its Relevance to Depression and Posttraumatic Stress Disorder in Humans: A Meta-Analysis

Abstract

The research on molecular causes of stress-associated psychopathologies is becoming highly important because the number of people with depression, generalized anxiety disorder and posttraumatic stress disorders (PTSDs) is steadily increasing every year. Investigation of molecular mechanisms in animal models opens up broad prospects for researchers, but relevant molecular signatures can differ significantly between patients and animal models. In our work, we for the first time carried out a meta-analysis of transcriptome changes in the prefrontal cortex of C57BL/6 mice after 10 and 30 days of social defeat stress (SDS). We then examined possible correlations of these alterations with transcriptome changes found in post-mortem samples from patients with depression or PTSD. Although transcriptional signatures of human psychiatric disorders and SDS did not overlap substantially, our results allowed us to identify the most reproducible changes seen after SDS of various durations. In addition, we were able to identify the genes involved in susceptibility to SDS after 10 days of stress. Taken together, these data help us to elucidate the molecular changes induced by SDS depending on its duration as well as their relevance to the alterations found in depression or PTSD in humans.

Fear circuit–based neurobehavioral signatures mirror resilience to chronic social stress in mouse

“…The characteristics of the Discriminating-avoiders, i.e., successful learning of threat-associated cues, threat–safety discrimination, and responsiveness to extinction of negative memories, are all discussed as characteristics of stress-resilient individuals ( 7 ). In contrast, generalized aversive responses and resistance to extinction after the occurrence of traumatic events, as seen by the Indiscriminate-avoiders , are key symptoms of stress-related mental disorders such as anxiety disorders ( 7 , 23 – 35 ) and thus, are characteristic of stress-susceptible individuals ( Fig. 2 ).…”

“…In the mPFC, most DEGs specific to the stress-susceptible Indiscriminate-avoiders subgroup were hemoglobin-associated transcripts and genes encoding for proteins involved in vascular integrity and function. According to a recent meta-analysis, hemoglobin genes are among the most consistently regulated genes following a 10-d CSD ( 32 ). Hemoglobin expression is present in neurons ( 33 ), and recent findings suggest their specific involvement in neurodegenerative disorders ( 34 ).…”

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

“…3A ). Recently, it has been revealed that most of the differentially expressed genes in the prefrontal cortex of depressed patients are immediate early genes such as Nr4a3 [ 38 ]. In line with these findings, several immediate early genes such as Nr4a3 were up‐regulated in the kidney of defeated male C57 BL/6 mice (Fig.…”

“…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).…”

Once induced, it lasts for a long time: the structural and molecular signatures associated with depressive-like behavior after neonatal immune activation

“…These differences are seen both in the neonatal period—when the stage of development of the brain in rats and mice corresponds to the stage of development of the third trimester of pregnancy in humans (Lupien et al, 2009 )—and in adulthood because it is not yet possible to unambiguously match various regions of the cerebral cortex between rodents and humans. This may be the reason for the inconsistency among results of comparisons of transcriptional signatures between various mouse models of depression and postmortem data from patients with MDD (Scarpa et al, 2020 ; Reshetnikov et al, 2022 ).…”