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 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 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 Deficits in hippocampal-dependent memory across different rodent models of early life stress: systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariana Rocha ◽  
Daniel Wang ◽  
Victor Avila-Quintero ◽  
Michael H. Bloch ◽  
Arie Kaffman
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Dorsal Hippocampus ◽  
Meta Analysis ◽  
Early Life Stress ◽  
Ventral Hippocampus ◽  
Contextual Fear Conditioning ◽  
Rodent Models ◽  
Improved Performance

AbstractExposure to early life stress (ELS) causes abnormal hippocampal development and functional deficits in rodents and humans, but no meta-analysis has been used yet to quantify the effects of different rodent models of ELS on hippocampal-dependent memory. We searched PubMed and Web of Science for publications that assessed the effects of handling, maternal separation (MS), and limited bedding and nesting (LBN) on performance in the Morris water maze (MWM), novel object recognition (NOR), and contextual fear conditioning (CFC). Forty-five studies met inclusion criteria (n = 451–763 rodents per test) and were used to calculate standardized mean differences (Hedge’s g) and to assess heterogeneity, publication bias, and the moderating effects of sex and species (rats vs. mice). We found significantly lower heterogeneity in LBN compared to handling and MS with no consistent effects of sex or species across the three paradigms. LBN and MS caused similar cognitive deficits in tasks that rely heavily on the dorsal hippocampus, such as MWM and NOR, and were significantly different compared to the improved performance seen in rodents exposed to handling. In the CFC task, which relies more on the ventral hippocampus, all three paradigms showed reduced freezing with moderate effect sizes that were not statistically different. These findings demonstrate the utility of using meta-analysis to quantify outcomes in a large number of inconsistent preclinical studies and highlight the need to further investigate the possibility that handling causes different alterations in the dorsal hippocampus but similar outcomes in the ventral hippocampus when compared to MS and LBN.

scholarly journals Early-life stress induces genome-wide sex-dependent miRNA expression and correlation across limbic brain areas in rats

Epigenomics ◽  
2021 ◽  
Author(s):  
Lauren A McKibben ◽  
Yogesh Dwivedi
Keyword(s):  
Prefrontal Cortex ◽  
Mirna Expression ◽  
Life Stress ◽  
Early Life ◽  
Target Genes ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Small Rna Sequencing ◽  
Dependent Manner ◽  
Genome Wide

Aims: The aim of this study was to assess regional- and sex-dependent changes in miRNA expression resulting from early-life stress (ELS). Materials and methods: Small RNA sequencing was used to determine sex-dependent changes in miRNAs after maternal separation, a rodent model of ELS, across the prefrontal cortex, amygdala and hippocampus. Results: Maternal separation induced anhedonia and altered miRNA expression in a sex-dependent manner, particularly in the prefrontal cortex and hippocampus. Gene ontology revealed that these miRNAs target genes with brain-specific biological functions. Conclusions: Using a network approach to explore miRNA signaling across the brain after ELS, regional differences were highlighted as key to studying the brain’s stress response, which indicates that sex is critical for understanding miRNA-mediated ELS-induced behavior.

Developmental effects of early-life stress on dopamine D2 receptor and proteins involved in noncanonical D2 dopamine receptor signaling pathway in the prefrontal cortex of male rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maryam Mahmoodkhani ◽  
Maedeh Ghasemi ◽  
Leila Derafshpour ◽  
Mohammad Amini ◽  
Nasrin Mehranfard
Keyword(s):  
Prefrontal Cortex ◽  
Young Adult ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
D2 Receptor ◽  
Early Life Stress ◽  
Adolescent And Young Adult ◽  
Male Rats ◽  
Gsk 3Β

Abstract Objectives Dopamine neurotransmission is implicated in multiple neuropsychiatric disorders, most strikingly in Parkinson’s disease, bipolar disorder, attention-deficit hyperactivity disorder and schizophrenia. In addition to canonical pathway, D2-receptor (D2R) exerts some of its biological actions through regulating the activity of Akt and GSK3, which in turn were found to be altered in several psychiatric illnesses. The present study examined the impacts of maternal separation, an early-life stress model which has been associated with disturbed neurodevelopment and appearance of many psychiatric disorders, on developmental changes in dopamine concentration and the expression of D2Rs, Akt and GSK-3β in the medial prefrontal cortex (PFC; a key target of stress) in adolescent and young adult male rats. Methods Maternal separation was performed 3 h per day from postnatal days 2 to 11. The PFC protein and dopamine contents were determined using western blotting analysis and Eliza, respectively. Results Results indicated long-term increases in the prefrontal dopamine levels in stressed adolescent and young adult male rats, accompanied by significant downregulation of D2R as well as upregulation of p-Akt and GSK-3β contents in stressed adolescence compared to controls, with all protein levels that returned to control values in stressed adult rats. Conclusions Our findings suggest that early-life stress differentially modulates prefrontal D2R/Akt/GSK-3β levels during development. Since adolescence period is susceptible to the onset of specific mental illnesses, disruption of noncanonical components of D2R signaling during this critical period may have an important role in programming neurobehavioral phenotypes in adulthood and manipulations influencing Akt/GSK-3β pathway may improve the expression of specific dopamine-related behaviors and the effects of dopaminergic drugs.

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 disrupts social behavior and prefrontal cortex parvalbumin interneurons at an earlier time-point in females than in males

2014 ◽  
Vol 566 ◽  
pp. 131-136 ◽  
Author(s):  
Freedom H. Holland ◽  
Prabarna Ganguly ◽  
David N. Potter ◽  
Elena H. Chartoff ◽  
Heather C. Brenhouse
Keyword(s):  
Prefrontal Cortex ◽  
Social Behavior ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Parvalbumin Interneurons ◽  
Time Point

scholarly journals Early-life stress diminishes the increase in neurogenesis after exercise in adult female mice

Hippocampus ◽  
2017 ◽  
Vol 27 (8) ◽  
pp. 839-844 ◽  
Author(s):  
M. R. Abbink ◽  
E. F. G. Naninck ◽  
P. J. Lucassen ◽  
A. Korosi
Keyword(s):  
Adult Female ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Mice
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