A novel mouse model of postpartum depression using emotional stress as evaluated by nesting behavior
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ABSTRACT:
SUBMITTER: Seki T
PROVIDER: S-EPMC8604943 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Postpartum depression is a complex illness that often occurs in genetically predisposed individuals. Closely related inbred rat strains are a great resource to identify novel causative genes and mechanisms underlying complex traits such as postpartum behavior. We report differences in these behaviors between the inbred depression model, Wistar Kyoto (WKY) More Immobile (WMI), and the isogenic control Wistar Kyoto Less Immobile (WLI) dams. WMI dams showed significantly lower litter survival rate and frequency of arched back and blanket nursing, but increased pup-directed licking, grooming, and retrieval during postpartum days (PPD) 1-10, compared to control WLIs. This increased pup-directed behavior and the frequency of self-directed behaviors segregated during selective breeding of the progenitor strain of WKY, which is also a depression model. These behaviors are manifested in the WMIs in contrast to those of WLIs. Furthermore, habitual differences in the self-directed behavior between light and dark cycles present in WLIs were missing in WMI dams. Hypothalamic transcript levels of the circadian rhythm-related gene Lysine Demethylase 5A (Kdm5a), period 2 (Per2), and the maternal behavior-related oxytocin receptor (Oxtr), vasopressin (Avp), and vasopressin receptor 1a (Avpr1a) were significantly greater in the post-weaning WMI dams at PPD 24 compared to those of WLIs, and also to those of WMI dams whose litter died before PPD 5. Expression correlation amongst genes differed in WLI and WMI dams and between the two time-points postpartum, suggesting genetic and litter-survival differences between these strains affect transcript levels. These data demonstrate that the genetically close, but behaviorally disparate WMI and WLI strains would be suitable for investigating the underlying genetic basis of postpartum behavior.
| S-EPMC7649805 | biostudies-literature
Project description:The exon-52-deleted mdx52 mouse is a critical model of Duchenne muscular dystrophy (DMD), as it features a deletion in a hotspot region of the DMD gene, frequently mutated in patients. Deletion of exon 52 impedes expression of several brain dystrophins (Dp427, Dp260 and Dp140), thus providing a key model for studying the cognitive impairment associated with DMD and testing rescuing strategies. Here, using in vivo magnetic resonance imaging and neurohistology, we found no gross brain abnormalities in mdx52 mice, suggesting that the neural dysfunctions in this model are likely at the level of brain cellular functionalities. Then, we investigated emotional behavior and fear learning performance of mdx52 mice compared to mdx mice that only lack Dp427 to focus on behavioral phenotypes that could be used in future comparative preclinical studies. mdx52 mice displayed enhanced anxiety and a severe impairment in learning an amygdala-dependent Pavlovian association. These replicable behavioral outcome measures are reminiscent of the internalizing problems reported in a quarter of DMD patients, and will be useful for preclinical estimation of the efficacy of treatments targeting brain dysfunctions in DMD.
| S-EPMC8476816 | biostudies-literature
Project description:Postpartum psychosis (PP) is a severe psychiatric disorder affecting a small proportion of new mothers shortly after childbirth. The molecular pathophysiology underlying the disorder is currently poorly understood, and there are no amenable animal models for the condition; maternal deficiency for the enzyme steroid sulfatase has been proposed as a potential risk mechanism. Here we show that inhibition of steroid sulfatase with 667-COUMATE (10mg/kg p.o.) in new mouse mothers results in behavioural abnormalities that can be partially alleviated by the administration of the clinically-efficacious antipsychotic ziprasidone (0.3-1.0mg/kg i.p.). The pattern of behavioural abnormalities in 667-COUMATE-treated mice implicated a genetic substrate at 21-23cM on chromosome 15; of the 17 genes within this chromosomal interval, only one (Nov/Ccn3) was significantly differentially expressed in the brains of vehicle and 667-COUMATE-treated mice. Two additional members of the Ccn family (Ccn2/Ctgf and Ccn4/Wisp1) were also significantly differentially expressed between the two groups, as were three further genes co-expressed with Nov/Ccn3 in brain (Arhgdig) or previously implicated in disorder risk by clinical studies (Adcy8 and Ccl2). The expression of Nov/Ccn3, but not of the other differentially-expressed genes, could be normalised by ziprasidone administration (1.0mg/kg). NOV/CCN3 lies directly under a linkage peak for PP risk at 8q24, and the associated protein possesses numerous characteristics that make it an excellent candidate mediator of PP risk. Our data suggest the 667-COUMATE-treated mouse as a model for PP with some degree of face, construct, and predictive validity, and implicate a novel, and biologically-plausible, molecular risk pathway for PP.
| S-EPMC5094271 | biostudies-literature
Project description:BackgroundSteroid sulfatase (STS) cleaves sulfate groups from steroid hormones; its expression/activity increases in late pregnancy and into the postpartum period. STS-deficient human and mouse mothers display elevated psychopathology and abnormal behaviour respectively; in mice, these effects can be partially normalised by antipsychotic (ziprasidone) administration.MethodologyWe compared brain gene expression in new mouse mothers administered the STS inhibitor 667-Coumate, or vehicle; significant changes were followed-up with pathway analysis and quantitative polymerase chain reaction (qPCR). Finally, the effects of combined 667-Coumate and ziprasidone administration on expression of the most robustly differentially-expressed genes were examined.ResultsSurprisingly, no between-group gene expression changes were detected at a False Discovery Rate (FDR)-corrected p<0.1. 1,081 unique expression changes were detected at p<0.05, two top hits were verified by qPCR, and pathway analysis indicated enrichment of genes involved in olfactory transduction. The expression of Stoml3 and Cyp2g1 was unaffected by ziprasidone administration.ConclusionsPostpartum behavioural abnormalities in STS-deficient mothers are likely to be the culmination of many small gene expression changes. Our data are consistent with the idea that olfactory function is key to maternal behaviour in mice, and suggest that aberrant expression of olfactory system genes may underlie abnormal maternal behaviour in STS-deficient women.
| S-EPMC6689211 | biostudies-literature
Project description:Perinatal stress, anxiety, and depression impacts not only women but also their child(ren). The purpose of this longitudinal study is to explore trends of stress, anxiety, and depressive symptoms from pregnancy to postpartum and understand predictions of stress and anxiety on postpartum depression. One-hundred-fifty-six women at 23-28 weeks gestation (T1), 147 at 32-36 weeks gestation (T2), 129 at over 36 weeks gestation (T3), and 83 at postpartum (T4) completed study surveys. The Perceived Stress Scale, Center for Epidemiologic Studies Depression scale, and State-Trait Anxiety Inventory were used to measure stress, depressive symptoms, and anxiety. Descriptive statistics, Pearson and Spearman's correlation, and Generalized Estimating Equation were applied to analyze the data. Results showed that levels of anxiety and depressive symptoms increased from 24 weeks gestation to postpartum, whereas stress levels decreased during pregnancy but increased in postpartum. Over half of women experienced anxiety symptoms, especially during late pregnancy and postpartum. Stress, anxiety, and depressive symptoms were inter-correlated. Notably, women at late pregnancy and postpartum were prone to stress, anxiety, and depression. Prenatal anxiety could predict postpartum depressive symptoms. Active assessment and management of stress, anxiety, and depression is needed and should begin from early pregnancy and continue until postpartum.
| S-EPMC8431252 | biostudies-literature
Project description:RNA-sequencing of the orbitofrontal cortex was performed in male and female rats following exposure to the limited bedding and nesting model of early life adversity.
2024-06-08 | GSE176488 | GEO
Project description:Cystic fibrosis (CF) patients experience heightened levels of anxiety and depression. Stress from dealing with chronic disease and rigorous treatment regimens certainly are primary contributors to these outcomes. We previously have demonstrated that microtubule alterations in CF are linked to a number of CF phenotypes including growth regulation and inflammatory responses to airway bacterial challenge. Deletion of histone deactelyase 6 (HDAC6), a cytosolic deacetylase that regulates tubulin acetylation, in CF mice restores growth and inflammatory phenotypes to wild type (WT) profiles. In this study, the hypothesis that Hdac6 depletion in CF mice would impact behaviors since Hda6 inhibition has been previously reported to have anti-depressive properties. Data demonstrate that CF mice exhibit reduced activity and reduced open arm time in an elevated plus maze test which can be consistent with anxiety-like behavior. CF mice also exhibit depression-like behaviors compared to WT mice in an age dependent manner. By eight weeks of age, CF mice exhibit significantly more immobile time in the tail-suspension test, however, Hdac6 depletion reverses the depressive phenotype. These data demonstrate that loss of CFTR function may predispose patients to experience depression and that this behavior is Hdac6 dependent.
| S-EPMC7530985 | biostudies-literature
Project description:Acute stress has been linked with prosocial behavior, yet it is entirely unexplored how different types of stressors may affect individuals' willingness to help: This is particularly relevant while people is experiencing multiple sources of stress due to the COVID-19 pandemic. Here we explore whether different types of stress influence peoples' giving behavior and the moderating role of emotional intelligence (EI). Undergraduate students were exposed to experimentally induced social, cognitive, or emotional stress and were asked to self-report on their willingness to help and donate to a charity raising funds for COVID-19 and flu patients. Results showed that when compared to a control condition, after being exposed to a social stress, participants were more willing to help a person in need. Our results also provide evidence that, after experiencing a social stress, participants with high (vs low) trait EI were more willing to help, and, as a result, donated more. Findings indicate that moderate levels of distress are associated with increased donations. Interestingly, when stress is not too threatening, high EI can regulate it and promote prosocial behaviors.
| S-EPMC8907929 | biostudies-literature
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.
| S-EPMC5530055 | biostudies-other
Project description:Adult neurogenesis has been implicated in affective disorders and the action of antidepressants (ADs) although the functional significance of this association is still unclear. The use of animal models closely mimicking human comorbid affective and anxiety disorders seen in the majority of patients should provide relevant novel information. Here, we used a unique genetic mouse model displaying higher trait anxiety (HAB) and comorbid depression-like behavior. We demonstrate that HABs have a lower rate of hippocampal neurogenesis and impaired functional integration of newly born neurons as compared with their normal anxiety/depression-like behavior (NAB) controls. In HABs, chronic treatment with the AD fluoxetine alleviated their higher depression-like behavior and protected them from relapse for 3 but not 7 weeks after discontinuation of the treatment without affecting neurogenesis. Similar to what has been observed in depressed patients, fluoxetine treatment induced anxiogenic-like effects during the early treatment phase in NABs along with a reduction in neurogenesis. On the other hand, treatment with AD drugs with a particularly strong anxiolytic component, namely the neurokinin-1-receptor-antagonist L-822?429 or tianeptine, increased the reduced rate of neurogenesis in HABs up to NAB levels. In addition, challenge-induced hypoactivation of dentate gyrus (DG) neurons in HABs was normalized by all three drugs. Overall, these data suggest that AD-like effects in a psychopathological mouse model are commonly associated with modulation of DG hypoactivity but not neurogenesis, suggesting normalization of hippocampal hypoactivity as a neurobiological marker indicating successful remission. Finally, rather than to higher depression-related behavior, neurogenesis seems to be linked to pathological anxiety.
| S-EPMC3565824 | biostudies-other