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A novel mouse model of postpartum depression using emotional stress as evaluated by nesting behavior.

ABSTRACT: Postpartum depression is an important mental health issue not only for the mother but also for the child's development, other family members, and the society. An appropriate animal model is desired to elucidate the pathogenesis of postpartum depression. However, methods for stress loading during pregnancy have not been established. Behavioral experiments to investigate postpartum depression-like behaviors should be conducted without stress because behavioral tests affect rearing behaviors such as lactation. Therefore, we developed a new mouse model of postpartum depression using a psychological stress method. Mating partners were made to witness their partners experiencing social defeat stress and then listen to their cries. Emotional stress loading during pregnancy significantly increased postpartum depression-like behaviors. Postpartum depression also affected nurturing behaviors and caused disturbances in pup care. Furthermore, nesting behavior was impaired in the stressed group, suggesting that the observation of nesting behavior may be useful for assessing social dysfunction in postpartum depression. These results demonstrate the utility of this new mouse model of postpartum depression.

SUBMITTER: Seki T

PROVIDER: S-EPMC8604943 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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A novel mouse model of postpartum depression using emotional stress as evaluated by nesting behavior.

Seki Tomoe T Yamagata Hirotaka H Uchida Shusaku S Kobayashi Ayumi A Watanabe Yoshifumi Y Nakagawa Shin S

Scientific reports 20211119 1

Postpartum depression is an important mental health issue not only for the mother but also for the child's development, other family members, and the society. An appropriate animal model is desired to elucidate the pathogenesis of postpartum depression. However, methods for stress loading during pregnancy have not been established. Behavioral experiments to investigate postpartum depression-like behaviors should be conducted without stress because behavioral tests affect rearing behaviors such a ...[more]

PMID: 34799651

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Project description:Gulf War Illness (GWI) is a chronic multisymptom disorder that affects approximately 25-32% of Gulf War veterans and is characterized by a number of symptoms such as cognitive impairment, psychiatric disturbances, chronic fatigue and gastrointestinal distress, among others. While the exact etiology of GWI is unknown, it is believed to have been caused by toxic exposures encountered during deployment in combination with other factors such as stress. In the present study we sought to evaluate the hypothesis that exposure to the toxin permethrin could prime neuroinflammatory stress response and elicit psychiatric symptoms associated with GWI. Specifically, we developed a mouse model of GWI, to evaluate the effects of chronic permethrin exposure followed by unpredictable stress. We found that subjecting mice to 14 days of chronic permethrin exposure followed by 7 days of unpredictable stress resulted in the development of depression-like behavior. This behavioral change coincided with distinct alterations in the microglia phenotype, indicating microglial activation in the hippocampus. We revealed that blocking microglial activation through Gi inhibitory DREADD receptors in microglia effectively prevented the behavioral change associated with permethrin and stress exposure. To elucidate the transcriptional networks impacted within distinct microglia populations linked to depression-like behavior in mice exposed to both permethrin and stress, we conducted a single-cell RNA sequencing analysis using 21,566 single nuclei collected from the hippocampus of mice. For bioinformatics, UniCell Deconvolve was a pre-trained, interpretable, deep learning model used to deconvolve cell type fractions and predict cell identity across spatial datasets. Our bioinformatics analysis identified significant alterations in permethrin exposure followed by stress-associated microglia population, notably pathways related to neuronal development, neuronal communication, and neuronal morphogenesis, all of which are associated with neural synaptic plasticity. Additionally, we observed permethrin exposure followed by stress-mediated changes in signal transduction, including modulation of chemical synaptic transmission, regulation of neurotransmitter receptors, and regulation of postsynaptic neurotransmitter receptor activity, a known contributor to the pathophysiology of depression in a subset of the hippocampal pyramidal neurons in CA3 subregions. Our findings tentatively suggest that permethrin may prime microglia towards a state of inflammatory activation that can be triggered by psychological stressors, resulting in depression-like behavior and alterations of neural plasticity. These findings underscore the significance of synergistic interactions between multi-causal factors associated with GWI.

Project description:Many studies have discovered a number of factors that can contribute to the risk of developing postpartum depression (PPD), including, but not limited to, life stressors, lack of social support, low economic status, and quality of the marital relationship. However, these studies were conducted in various countries with participants from different cultural backgrounds.This study aimed to examine the impact of general help-seeking behavior (GHSB) and partner support (PS) on PPD among Saudi women in primary health care clinics in Riyadh city.Data were collected by using self-administered measures of the Edinburgh Postnatal Depression Scale (EPDS), General Help-Seeking Questionnaire (GHSQ), and Partner Support Scale (PSS). Frequency distribution was used to analyze the categorical data, and Student's t-test and one-way analysis of variance were employed to compare the numerical data. Linear regression analysis was used to control for all confounders.The findings showed that 9% and 28% of women had good and poor GHSB, respectively, 16% had poor PS, and 25.7% could be classified as probably depressed. Negative relationships between GHSB versus PPD and PS versus PPD were observed. Adjusting by mode of delivery and controlling for confounders in linear regression showed that women who underwent normal vaginal delivery, with higher para rates (β=0.250, t=2.063) and lower PS scores (β=-0.238, t=-2.038), were more likely to suffer higher depression scores (adj P=0.043 and adj P=0.045, respectively). Women who underwent cesarean-section, with postpartum duration ≥6 weeks (β=0.374, t=2.082), were more likely to suffer higher depression scores (adj P=0.045) compared to those with <6 weeks of postpartum duration.The prevalence of PPD among the study participants was high, especially among higher para women who underwent normal delivery and women ≥6 weeks post cesarean-section, in comparison with the results in other studies. PPD is reduced by enhancing women's GHSB and PS.

Dataset Information

A novel mouse model of postpartum depression using emotional stress as evaluated by nesting behavior.

Publications

A novel mouse model of postpartum depression using emotional stress as evaluated by nesting behavior.

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