scholarly journals MeCP2 haplodeficiency and early-life stress interaction on anxiety-like behavior in adolescent female mice

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
María Abellán-Álvaro ◽  
Oliver Stork ◽  
Carmen Agustín-Pavón ◽  
Mónica Santos
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Hypothalamic Nucleus ◽  
Corticotropin Releasing Hormone ◽  
Wild Type ◽  
Releasing Hormone ◽  
Complex Disorders ◽  
Female Mice

Abstract Background Early-life stress can leave persistent epigenetic marks that may modulate vulnerability to psychiatric conditions later in life, including anxiety, depression and stress-related disorders. These are complex disorders with both environmental and genetic influences contributing to their etiology. Methyl-CpG Binding Protein 2 (MeCP2) has been attributed a key role in the control of neuronal activity-dependent gene expression and is a master regulator of experience-dependent epigenetic programming. Moreover, mutations in the MECP2 gene are the primary cause of Rett syndrome and, to a lesser extent, of a range of other major neurodevelopmental disorders. Here, we aim to study the interaction of MeCP2 with early-life stress in variables known to be affected by this environmental manipulation, namely anxiety-like behavior and activity of the underlying neural circuits. Methods Using Mecp2 heterozygous and wild-type female mice we investigated the effects of the interaction of Mecp2 haplodeficiency with maternal separation later in life, by assessing anxiety-related behaviors and measuring concomitant c-FOS expression in stress- and anxiety-related brain regions of adolescent females. Moreover, arginine vasopressin and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus were analyzed for neuronal activation. Results In wild-type mice, maternal separation caused a reduction in anxiety-like behavior and in the activation of the hypothalamic paraventricular nucleus, specifically in corticotropin-releasing hormone-positive cells, after the elevated plus maze. This effect of maternal separation was not observed in Mecp2 heterozygous females that per se show decreased anxiety-like behavior and concomitant decreased paraventricular nuclei activation. Conclusions Our data supports that MeCP2 is an essential component of HPA axis reprogramming and underlies the differential response to anxiogenic situations later in life.

scholarly journals Cerebral Erythropoietin Prevents Sex-Dependent Disruption of Respiratory Control Induced by Early Life Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Elizabeth Elliot-Portal ◽  
Christian Arias-Reyes ◽  
Sofien Laouafa ◽  
Rose Tam ◽  
Richard Kinkead ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Stress Hormones ◽  
Respiratory Control ◽  
Early Life Stress ◽  
Whole Body ◽  
Wild Type ◽  
Adult Mice ◽  
Respiratory Disturbance

Injuries that occur early in life are often at the root of adult illness. Neonatal maternal separation (NMS) is a form of early life stress that has persistent and sex-specific effects on the development of neural networks, including those that regulate breathing. The release of stress hormones during a critical period of development contributes to the deleterious consequences of NMS, but the role of increased corticosterone (CORT) in NMS-induced respiratory disturbance is unknown. Because erythropoietin (EPO) is a potent neuroprotectant that prevents conditions associated with hyperactivation of the stress neuroaxis in a sex-specific manner, we hypothesized that EPO reduces the sex-specific alteration of respiratory regulation induced by NMS in adult mice. Animals were either raised under standard conditions (controls) or exposed to NMS 3 h/day from postnatal days 3–12. We tested the efficacy of EPO in preventing the effects of NMS by comparing wild-type mice with transgenic mice that overexpress EPO only in the brain (Tg21). In 7-days-old pups, NMS augmented CORT levels ~2.5-fold by comparison with controls but only in males; this response was reduced in Tg21 mice. Respiratory function was assessed using whole-body plethysmography. Apneas were detected during sleep; the responsiveness to stimuli was measured by exposing mice to hypoxia (10% O2; 15 min) and hypercapnia (5% CO2; 10 min). In wild-type, NMS increased the number of apneas and the hypercapnic ventilatory response (HcVR) only in males; with no effect on Tg21. In wild-type males, the incidence of apneas was positively correlated with HcVR and inversely related to the tachypneic response to hypoxia. We conclude that neural EPO reduces early life stress-induced respiratory disturbances observed in males.

scholarly journals Exacerbated obesogenic response in female mice exposed to early life stress is linked to fat depot-specific upregulation of leptin protein expression

2020 ◽  
Vol 319 (5) ◽  
pp. E852-E862
Author(s):  
Jacqueline R. Leachman ◽  
Mathew D. Rea ◽  
Dianne M. Cohn ◽  
Xiu Xu ◽  
Yvonne N. Fondufe-Mittendorf ◽  
...  
Keyword(s):  
Protein Expression ◽  
Fat Mass ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Disease Risk ◽  
Early Life Stress ◽  
Female Mice ◽  
Fat Depot ◽  
Leptin Expression

Early life stress (ELS) is an independent risk factor for increased BMI and cardiometabolic disease risk later in life. We have previously shown that a mouse model of ELS, maternal separation and early weaning (MSEW), exacerbates high-fat diet (HF)-induced obesity only in adult female mice. Therefore, the aim of this study was to investigate 1) whether the short- and long-term effects of HF on leptin expression are influenced by MSEW in a sex-specific manner and 2) the potential epigenetic mechanisms underlying the MSEW-induced changes in leptin expression. After 1 wk of HF, both MSEW male and female mice displayed increased fat mass compared with controls ( P < 0.05). However, only MSEW female mice showed elevated leptin mRNA expression in gonadal white adipose tissue (gWAT; P < 0.05). After 12 wk of HF, fat mass remained increased only in female mice ( P < 0.05). Moreover, plasma leptin and both leptin mRNA and protein expression in gWAT were augmented in MSEW female mice compered to controls ( P < 0.05), but not in MSEW male mice. This association was not present in subcutaneous WAT. Furthermore, among 16 CpG sites in the leptin promoter, we identified three hypomethylated sites in tissue from HF-fed MSEW female mice compared with controls (3, 15, and 16, P < 0.05). These hypomethylated sites showed greater binding of key adipogenic factors such as PPARγ ( P < 0.05). Taken together, our study reveals that MSEW superimposed to HF increases leptin protein expression in a sex- and fat depot-specific fashion. Our data suggest that the mechanism by which MSEW increases leptin expression could be epigenetic.

Early-life stress-induced anxiety-related behavior in adult mice partially requires forebrain corticotropin-releasing hormone receptor 1

2012 ◽  
Vol 36 (3) ◽  
pp. 2360-2367 ◽  
Author(s):  
Xiao-Dong Wang ◽  
Christiana Labermaier ◽  
Florian Holsboer ◽  
Wolfgang Wurst ◽  
Jan M. Deussing ◽  
...  
Keyword(s):  
Hormone Receptor ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Adult Mice

Blockade of corticotropin-releasing hormone receptor 1 attenuates early-life stress-induced synaptic abnormalities in the neonatal hippocampus

Hippocampus ◽  
2014 ◽  
Vol 24 (5) ◽  
pp. 528-540 ◽  
Author(s):  
Xue-Mei Liao ◽  
Xiao-Dun Yang ◽  
Jiao Jia ◽  
Ji-Tao Li ◽  
Xiao-Meng Xie ◽  
...  
Keyword(s):  
Hormone Receptor ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone

scholarly journals Effects of Early-Life Stress on Social and Anxiety-Like Behaviors in Adult Mice: Sex-Specific Effects

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Natalya P. Bondar ◽  
Arina A. Lepeshko ◽  
Vasiliy V. Reshetnikov
Keyword(s):  
Social Behavior ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Individual Behavior ◽  
Male And Female ◽  
Female Mice ◽  
Specific Effects ◽  
The Social

Stressful events in an early postnatal period have critical implications for the individual’s life and can increase later risk for psychiatric disorders. The aim of this study was to investigate the influence of early-life stress on the social behavior of adult male and female mice. C57Bl/6 mice were exposed to maternal separation (MS, 3 h once a day) or handling (HD, 15 min once a day) on postnatal day 2 through 14. Adult male and female mice were tested for social behavior in the social interaction test and for individual behavior in the plus-maze and open-field tests. Female mice exposed to maternal separation had increased social behavior and increased anxiety. MS male mice had no changes in social behavior but had significantly disrupted individual behavior, including locomotor and exploratory activity. Handling had positive effects on social behavior in males and females and decreased anxiety in males. Our results support the hypothesis that brief separation of pups from their mothers (handling), which can be considered as moderate stress, may result in future positive changes in behavior. Maternal separation has deleterious effects on individual behavior and significant sex-specific effects on social behavior.

scholarly journals Impact of mothers’ past experience and early-life stress on aggression and cognition in adult male mice

2018 ◽  
Author(s):  
V. Reshetnikov ◽  
Yu. Ryabushkina ◽  
N. Bondar
Keyword(s):  
Locomotor Activity ◽  
Adult Male ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Life Experience ◽  
Early Life Stress ◽  
Male Mice ◽  
Female Mice ◽  
Stressful Experience

AbstractEarly life is an important period for brain development and behavioral programming. Both reduced maternal care and stress in early life are risk factors for various psychiatric disorders. Here, we hypothesized that females’ stressful experience in their early life can lead to a disruption of mother-offspring interactions toward their own progeny. The objective of this study is to assess the effects of mothers’ past stressful experience, early-life stress alone or both on behavior in adult male mice. In this study, female mice were allowed to raise their pups either without exposure to stress (normal rearing condition, NC) or with exposure to maternal separation (3h/day, maternal separation, MS) on postnatal days 2–14. Adult F1 female mice who had experienced MS (stressed mothers, SM) or had been reared normally (undisturbed mothers, UM) were used for generating F2 offspring to be or not to be further exposed to early-life stress. We assessed anxiety-like behavior, exploratory activity, locomotor activity, aggression and cognition in four groups of adult F2 males (UM+NC, UM+MS, SM+NC, SM+MS). We found that SM+MS males become more aggressive if agonistic contact is long enough, suggesting a change in their social coping strategy. Moreover, these aggressive males tended to improve longterm spatial memory. Aggressive SM+NC males, in contrast, showed learning impairments. We did not find any significant differences in anxiety-like behavior or exploratory and locomotor activity. Overall, our findings suggest that mothers’ early-life experience may have important implications for the adult behavior of their offspring.

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