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 Maternal Separation Early in Life Alters the Expression of Genes Npas4 and Nr1d1 in Adult Female Mice: Correlation with Social Behavior

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Yuliya A. Ryabushkina ◽  
Vasiliy V. Reshetnikov ◽  
Natalya P. Bondar
Keyword(s):  
Prefrontal Cortex ◽  
Social Behavior ◽  
Adult Female ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Dorsal Hippocampus ◽  
Early Life Stress ◽  
Female Mice ◽  
History Of

Early-life stress affects neuronal plasticity of the brain regions participating in the implementation of social behavior. Our previous studies have shown that brief and prolonged separation of pups from their mothers leads to enhanced social behavior in adult female mice. The goal of the present study was to characterize the expression of genes (which are engaged in synaptic plasticity) Egr1, Npas4, Arc, and Homer1 in the prefrontal cortex and dorsal hippocampus of adult female mice with a history of early-life stress. In addition, we evaluated the expression of stress-related genes: glucocorticoid and mineralocorticoid receptors (Nr3c1 and Nr3c2) and Nr1d1, which encodes a transcription factor (also known as REVERBα) modulating sociability and anxiety-related behavior. C57Bl/6 mice were exposed to either maternal separation (MS, 3 h once a day) or handling (HD, 15 min once a day) on postnatal days 2 through 14. In adulthood, the behavior of female mice was analyzed by some behavioral tests, and on the day after the testing of social behavior, we measured the gene expression. We found increased Npas4 expression only in the prefrontal cortex and higher Nr1d1 expression in both the prefrontal cortex and dorsal hippocampus of adult female mice with a history of MS. The expression of the studied genes did not change in HD female mice. The expression of stress-related genes Nr3c1 and Nr3c2 was unaltered in both groups. We propose that the upregulation of Npas4 and Nr1d1 in females with a history of early-life stress and the corresponding enhancement of social behavior may be regarded as an adaptation mechanism reversing possible aberrations caused by early-life stress.

scholarly journals Cocaine-Induced Impulsivity is Differentially Expressed in Male and Female Mice Exposed to Maternal Separation and is Associated with Alterations in AMPA Receptors Subunits

2020 ◽  
Author(s):  
Adriana Castro-Zavala ◽  
Ana Martin-Sanchez ◽  
Larisa Montalvo-Martínez ◽  
Alberto Camacho-Morales ◽  
Olga Valverde
Keyword(s):  
Protein Expression ◽  
Ampa Receptors ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Cocaine Seeking

ABSTRACTImpulsivity is a key trait in the diagnosis of major depressive disorder (MDD) and substance use disorder (SUD). MDD is a chronic illness characterized by sadness, insomnia, and loss of interest. SUD is a chronic and relapsing disorder characterized by the consumption of drugs despite their negative consequences. Among drugs of abuse, cocaine is the most consumed psychostimulant. Animal studies demonstrated that increased impulsivity predicts predisposition to acquire cocaine self-administration (SA) behaviour with an increased cocaine-intake. Moreover, early-life stress represents a vulnerability factor to develop depressive disorders and drug addiction. Maternal separation with early weaning (MSEW) is an animal model that allows examining the impact of early-life stress on cocaine abuse. In this study, we aimed to explore changes in MSEW-induced impulsivity to determine potential associations between depression-like and cocaine-seeking behaviours in male and female mice. We also evaluated possible alterations in the AMPA receptors (AMPArs) composition and glutamatergic neurotransmission. We exposed mice to MSEW and the behavioural tests were performed during adulthood. Moreover, GluA1, GluA2 mRNA and protein expression were evaluated in the medial Prefrontal Cortex (mPFC). Results showed higher impulsive cocaine-seeking in females, independently the MSEW, as well as an increase in GluA1 and GluA2 protein expression. Moreover, MSEW induced downregulation of Gria2 and increased the GluA1/GluA2 ratio, only in male mice. In conclusion, female mice expressed higher mPFC glutamatergic function, which potentiated their impulsivity during cocaine SA. Also, data indicated that MSEW alters glutamatergic function in mPFC of male mice, increasing the glutamatergic excitability.

scholarly journals Early life stress alters transcriptomic patterning across reward circuitry in male and female mice

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Catherine Jensen Peña ◽  
Milo Smith ◽  
Aarthi Ramakrishnan ◽  
Hannah M. Cates ◽  
Rosemary C. Bagot ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Cortical Plasticity ◽  
Early Life Stress ◽  
Stress Sensitivity ◽  
Sensitive Period ◽  
Male And Female ◽  
Reward Circuitry ◽  
Female Mice ◽  
Increase Risk

Abstract Abuse, neglect, and other forms of early life stress (ELS) significantly increase risk for psychiatric disorders including depression. In this study, we show that ELS in a postnatal sensitive period increases sensitivity to adult stress in female mice, consistent with our earlier findings in male mice. We used RNA-sequencing in the ventral tegmental area, nucleus accumbens, and prefrontal cortex of male and female mice to show that adult stress is distinctly represented in the brain’s transcriptome depending on ELS history. We identify: 1) biological pathways disrupted after ELS and associated with increased behavioral stress sensitivity, 2) putative transcriptional regulators of the effect of ELS on adult stress response, and 3) subsets of primed genes specifically associated with latent behavioral changes. We also provide transcriptomic evidence that ELS increases sensitivity to future stress through enhancement of known programs of cortical plasticity.

scholarly journals Early life stress alters transcriptomic patterning across reward circuitry in male and female mice

2019 ◽  
Author(s):  
Catherine Jensen Peña ◽  
Milo Smith ◽  
Aarthi Ramakrishnan ◽  
Hannah M. Cates ◽  
Rosemary C. Bagot ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Cortical Plasticity ◽  
Early Life Stress ◽  
Stress Sensitivity ◽  
Sensitive Period ◽  
Male And Female ◽  
Reward Circuitry ◽  
Female Mice ◽  
Increase Risk

ABSTRACTAbuse, neglect, and other forms of early life stress (ELS) significantly increase risk for psychiatric disorders including depression. In this study, we show that ELS in a postnatal sensitive period increases sensitivity to adult stress in female mice, consistent with our earlier findings in male mice. We used RNA-sequencing in the ventral tegmental area, nucleus accumbens, and prefrontal cortex of male and female mice to show that adult stress is distinctly represented in the brain’s transcriptome depending on ELS history. We identify: 1) biological pathways disrupted after ELS and associated with increased behavioral stress sensitivity, 2) putative transcriptional regulators of the effect of ELS on adult stress response, and 3) subsets of primed genes specifically associated with latent behavioral changes. We also provide transcriptomic evidence that ELS increases sensitivity to future stress through enhancement of known programs of cortical plasticity.

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 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.

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.

scholarly journals Early-Life Stress Modulates Gut Microbiota and Peripheral and Central Inflammation in a Sex-Dependent Manner

2021 ◽  
Vol 22 (4) ◽  
pp. 1899 ◽  
Author(s):  
Hae Jeong Park ◽  
Sang A. Kim ◽  
Won Sub Kang ◽  
Jong Woo Kim
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Female Rats ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Male And Female Rats

Recent studies have reported that changes in gut microbiota composition could induce neuropsychiatric problems. In this study, we investigated alterations in gut microbiota induced by early-life stress (ELS) in rats subjected to maternal separation (MS; 6 h a day, postnatal days (PNDs) 1–21), along with changes in inflammatory cytokines and tryptophan-kynurenine (TRP-KYN) metabolism, and assessed the differences between sexes. High-throughput sequencing of the bacterial 16S rRNA gene showed that the relative abundance of the Bacteroides genus was increased and that of the Lachnospiraceae family was decreased in the feces of MS rats of both sexes (PND 56). By comparison, MS increased the relative abundance of the Streptococcus genus and decreased that of the Staphylococcus genus only in males, whereas the abundance of the Sporobacter genus was enhanced and that of the Mucispirillum genus was reduced by MS only in females. In addition, the levels of proinflammatory cytokines were increased in the colons (IFN-γ and IL-6) and sera (IL-1β) of the male MS rats, together with the elevation of the KYN/TRP ratio in the sera, but not in females. In the hippocampus, MS elevated the level of IL-1β and the KYN/TRP ratio in both male and female rats. These results indicate that MS induces peripheral and central inflammation and TRP-KYN metabolism in a sex-dependent manner, together with sex-specific changes in gut microbes.

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