Brain activation induced by chronic psychosocial stress in mice

Laine, Mikaela; Sokołowska, Ewa; Dudek, Mateusz; Callan, Saija-Anita; Hyytiä, Petri; Hovatta, Iiris

doi:10.1038/s41598-017-15422-5

Cited by 65 publications

(48 citation statements)

References 60 publications

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“…Accumulation of ΔFosB is linked with repeated neuronal activation . Thus, these data suggest similar levels of repeated neuronal activity in the mPFC in males and females, regardless of hormonal condition or stress.…”

Section: Discussionmentioning

confidence: 53%

“…Hormonal manipulation or stress did not broadly influence the density of ΔFosB immunopositive cells in the mPFC in male or female rats. The results of several studies indicate chronic immobilisation (1 hour day ‐1 , 10 days) or restraint‐ associated (6 hour day ‐1 , 21 days)FosB induction in the mPFC in males, whereas others find no change in ΔFosB expression following chronic restraint (1 hour day ‐1 , 14 days), noise (30 minutes day ‐1 , 12 days) or social defeat‐ stress (10 minutes day ‐1 , 10 days) . Taken together, these studies suggest severity‐ and duration‐dependent effects of stress on ΔFosB induction.…”

Section: Discussionmentioning

confidence: 96%

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Gonadal hormones differentially regulate sex‐specific stress effects on glia in the medial prefrontal cortex

Bollinger

Salinas

Fender

et al. 2019

J Neuroendocrinology

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Women are more susceptible to various stress‐linked psychopathologies, including depression. Dysfunction of the medial prefrontal cortex (mPFC) has been implicated in depression, and studies indicate sex differences in stress effects on mPFC structure and function. For example, chronic stress induces dendritic atrophy in the mPFC in male rats, yet dendritic growth in females. Recent findings suggest glial pathways toward depression. Glia are highly responsive to neuronal activity and function as critical regulators of synaptic plasticity. Preclinical models demonstrate stress‐induced microglial activation in mPFC in males, yet deactivation in females. By contrast, stress reduces astrocyte complexity in mPFC in male rats, whereas the effects in females are unknown. Glia possess receptors for most gonadal hormones and gonadal hormones are known to modulate neuronal activity. Thus, gonadal hormones represent a potential mechanism underlying sex differences in glia, as well as divergent stress effects. Therefore, we examined the role of gonadal hormones in sex‐specific stress effects on neuronal activity (ie FosB/ ΔFosB induction) and glia in the mPFC. The findings obtained indicate greater microglial activation in mPFC in females and a greater astrocyte area in males. Basal astrocyte morphology is modulated by androgens, whereas androgens or oestrogens dampen the microglial state in males. Astrocyte morphology is associated with neuronal activity in both sexes, regardless of hormonal condition. Chronic stress induced astrocytic atrophy in males, yet hypertrophy in females, with gonadal hormones partly regulating this difference. Stress effects on microglia are oestradiol‐dependent in females. Taken together, these data suggest sex‐specific, gonadal hormone‐dependent stress effects on astrocytes and microglia in the mPFC.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 96%

Gonadal hormones differentially regulate sex‐specific stress effects on glia in the medial prefrontal cortex

Bollinger

Salinas

Fender

et al. 2019

J Neuroendocrinology

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“…The source of these alterations is unclear. For example, these may be due to stress causing sexdependent changes in the functional connections between or within these regions (e.g., neural activity, cellular and synaptic plasticity), or alterations in the activity of upstream molecular regulators of overlapping molecular signaling pathways 40,[46][47][48][49][50] . Another possibility is that transcriptional coherence between brain regions reflects resting state activity patterns, although this has not been experimentally tested.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in adult mood and in stress-induced transcriptional coherence across mesocorticolimbic circuitry

et al. 2020

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Women are approximately two times as likely to be diagnosed with major depressive disorder (MDD) compared to men. While sex differences in MDD might be driven by circulating gonadal hormones, we hypothesized that developmental hormone exposure and/or genetic sex might play a role. Mice were gonadectomized in adulthood to isolate the role of developmental hormones. We examined the effects of developmental gonadal and genetic sex on anhedonia-/depressive-like behaviors under non-stress and chronic stress conditions and performed RNA-sequencing in three mood-relevant brain regions. We used an integrative network approach to identify transcriptional modules and stress-specific hub genes regulating stress susceptibility, with a focus on whether these differed by sex. After identifying sex differences in anhedonia-/depressive-like behaviors (female > male), we show that both developmental hormone exposure (gonadal female > gonadal male) and genetic sex (XX > XY) contribute to the sex difference. The top biological pathways represented by differentially expressed genes were related to immune function; we identify which differentially expressed genes are driven by developmental gonadal or genetic sex. There was very little overlap in genes affected by chronic stress in males and females. We also identified highly co-expressed gene modules affected by stress, some of which were affected in opposite directions in males and females. Since all mice had equivalent hormone exposure in adulthood, these results suggest that sex differences in gonadal hormone exposure during sensitive developmental periods program adult sex differences in mood, and that these sex differences are independent of adult circulating gonadal hormones.

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“…It is interesting to compare the hyperconnectivity observed here to findings in other animal models used to investigate depression and anxiety. Brain activation in cortical and hippocampal regions in mice following chronic social defeat stress is observed in manganese-enhanced magnetic resonance imaging (Laine et al, 2017). Additionally, aberrant hippocampal, thalamic and cortical connectivity is reported in other rodent models using different data acquisition and/or analysis methods.…”

Section: Discussionmentioning

confidence: 99%

Validation of chronic restraint stress model in rats for the study of depression using longitudinal multimodal MR imaging

Seewoo

Hennessy

Feindel

et al. 2020

Preprint

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Prior research suggests that the neurobiological underpinnings of depression include disruptions in functional connectivity, neurometabolite levels, and hippocampal volume. This study examined the validity of a chronic restraint stress (CRS) paradigm in male Sprague Dawley rats for the study of depression using longitudinal behavioural tests and multiple 9.4 T MRI modalities (resting-state functional MRI, proton magnetic resonance spectroscopy, and volumetric studies). In the CRS protocol, rats were placed in individual transparent tubes for 2.5 h daily over 13 days. Elevated plus-maze test (EPM) and forced swim test (FST) confirmed the presence of anxiety-like and depression-like behaviours respectively post-restraint. Brain changes were also detected by MR. The rs-fMRI data revealed hypoconnectivity within the salience and interoceptive networks and hyperconnectivity of several brain regions to the cingulate cortex. The 1 H-MRS data revealed decreased sensorimotor cortical glutamate, glutamine and combined glutamate-glutamine levels. Volumetric analysis of T2-weighted images revealed decreased hippocampal volume, which was also correlated with salience network connectivity. Depression-like behaviours were correlated with salience and interoceptive network connectivity, glutamate and combined glutamate-glutamine levels and hippocampal volume. Anxiety-like behaviours were correlated with both hippocampus connectivity and interoceptive network connectivity. The present findings identify significant changes in brain connectivity, neurometabolites and structure that are correlated with abnormal behaviour in CRS rats. Importantly, these changes parallel those found in human depression, suggesting that the CRS rodent model has utility for translational studies and novel intervention development for depression.

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Brain activation induced by chronic psychosocial stress in mice

Cited by 65 publications

References 60 publications

Gonadal hormones differentially regulate sex‐specific stress effects on glia in the medial prefrontal cortex

Gonadal hormones differentially regulate sex‐specific stress effects on glia in the medial prefrontal cortex

Sex differences in adult mood and in stress-induced transcriptional coherence across mesocorticolimbic circuitry

Validation of chronic restraint stress model in rats for the study of depression using longitudinal multimodal MR imaging

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