Long-term Effects of Maternal Separation on Anxiety-Like Behavior and Neuroendocrine Parameters in Adult Balb/c Mice

Introduction: Disruption of maternal care using maternal separation (MS) models has provided significant evidence of the deleterious long-term effects of early life stress. Several preclinical studies investigating MS showed multiple behavioral and biomolecular alterations. However, there is still conflicting results from MS studies, which represents a challenge for reliability and replicability of those findings. Objective: To address that, this study was conducted to investigate whether MS would affect anxiety-like behaviors using a battery of classical tasks, as well as central and peripheral stress-related biomarkers. Methods: Male Balb/c mice were exposed to MS from postnatal day (PND) 2 to 14 for 180-min per day. Two independent cohorts were performed to evaluate both baseline and anxiety-like behavior responses to MS at PND60. We performed composite scores to evaluate MS effects on anxiety and risk assessment phenotypes. Also, we assessed mRNA gene expression in the medial pre-frontal cortex (mPFC) of glucocorticoid and mineralocorticoid receptors (GR and MR) using real-time PCR and peripheral corticosterone levels (CORT) to investigate possible neurobiological correlates to anxiety behaviors. Results: We found increased anxiety-like behavior and decreased risk assessment and exploratory behaviors in MS mice. The animals exposed to MS also presented a decrease in MR mRNA expression and higher levels of CORT compared to controls. Conclusions: Our findings reinforce the body of evidence suggesting that long-term MS induces effects on anxiety and risk assessment phenotypes following the exposure to a standardized MS protocol. Moreover, MS affected the expression of MR mRNA and induced significant changes on CORT response. This data highlights that the reprograming MS effects on HPA axis could be mediate by MR gene expression in mPFC and chronic overactivity of peripheral CORT levels.

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Long-Term Impact of Early-Life Stress on Hippocampal Plasticity: Spotlight on Astrocytes

International Journal of Molecular Sciences ◽

10.3390/ijms21144999 ◽

2020 ◽

Vol 21 (14) ◽

pp. 4999

Author(s):

Gürsel Çalışkan ◽

Anke Müller ◽

Anne Albrecht

Keyword(s):

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Early Life Stress ◽

Childhood Adversity ◽

Neuronal Circuits ◽

Long Term Effects ◽

Hippocampal Plasticity ◽

Local Circuits

Adverse experiences during childhood are among the most prominent risk factors for developing mood and anxiety disorders later in life. Early-life stress interventions have been established as suitable models to study the neurobiological basis of childhood adversity in rodents. Different models such as maternal separation, impaired maternal care and juvenile stress during the postweaning/prepubertal life phase are utilized. Especially within the limbic system, they induce lasting alterations in neuronal circuits, neurotransmitter systems, neuronal architecture and plasticity that are further associated with emotional and cognitive information processing. Recent studies found that astrocytes, a special group of glial cells, have altered functions following early-life stress as well. As part of the tripartite synapse, astrocytes interact with neurons in multiple ways by affecting neurotransmitter uptake and metabolism, by providing gliotransmitters and by providing energy to neurons within local circuits. Thus, astrocytes comprise powerful modulators of neuronal plasticity and are well suited to mediate the long-term effects of early-life stress on neuronal circuits. In this review, we will summarize current findings on altered astrocyte function and hippocampal plasticity following early-life stress. Highlighting studies for astrocyte-related plasticity modulation as well as open questions, we will elucidate the potential of astrocytes as new targets for interventions against stress-induced neuropsychiatric disorders.

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Early-life stress induces prodromal features of Parkinsonian with aging in rats

The Journals of Gerontology Series A ◽

10.1093/gerona/glab253 ◽

2021 ◽

Author(s):

Chao Ren ◽

Fen Wang ◽

Kai-Jie He ◽

Yu-Ting Zhang ◽

Ling-Xi Li ◽

...

Keyword(s):

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Early Life Stress ◽

Cell Counting ◽

Dopamine Level ◽

Long Term Effects ◽

Behavioral Alterations ◽

Transcriptional Changes

Abstract Early-life stress (ELS) can cause long-term effects on human health, ranging from adolescence to adulthood, and even to gerontic. Although clinical retrospective data suggest that ELS may be related to senile neurodegenerative diseases such as Parkinson’s disease (PD), there are few prospective investigations to explore its real contribution to PD. Here, we investigated the behavioral, histochemistical, neuromorphological and transcriptional changes induced by maternal separation (MS), an ELS model. Without neurotoxin, MS rats showed behavioral alterations in olfaction, locomotion and gait characters after depression compared with control rats. Based on neuroimaging and histochemistry, although we found that the dopaminergic system in striatum was impaired after MS, the decrease of striatal dopamine level was ~33%. Consistently, tyrosine hydroxylase immune-staining positive neurons of MS rats in the substantia nigra showed deficit by about 20% in cell counting. Furthermore, using transcriptome sequencing, we discovered many differentially expressed genes (DEGs) of MS rats in striatum significantly enriched in the pathway of dopaminergic synapse, and the biological process of locomotion and neuromuscular process controlling balance. Encouragingly, some representative DEGs relating to PD were singled out. These results suggest that ELS-depression rats potentially mimic some key features of prodromal stage of PD during natural senescence. In conclusion, our findings provide some novel insights into the future pathogenesis and therapeutic studies for PD related to depression.

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Long term effects of early life stress on HPA circuit in rodent models

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2020.111125 ◽

2021 ◽

Vol 521 ◽

pp. 111125

Author(s):

Lucy Babicola ◽

Rossella Ventura ◽

Sebastian Luca D'Addario ◽

Donald Ielpo ◽

Diego Andolina ◽

...

Keyword(s):

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Rodent Models ◽

Long Term Effects

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Maternal separation in rodents: a journey from gut to brain and nutritional perspectives

Proceedings of The Nutrition Society ◽

10.1017/s0029665119000958 ◽

2019 ◽

Vol 79 (1) ◽

pp. 113-132 ◽

Cited By ~ 3

Author(s):

Marion Rincel ◽

Muriel Darnaudéry

Keyword(s):

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Human Subjects ◽

Early Life Stress ◽

Long Term Effects ◽

Early Life Adversity ◽

Critical Window ◽

Beneficial Impact ◽

The Impact

The developmental period constitutes a critical window of sensitivity to stress. Indeed, early-life adversity increases the risk to develop psychiatric diseases, but also gastrointestinal disorders such as the irritable bowel syndrome at adulthood. In the past decade, there has been huge interest in the gut–brain axis, especially as regards stress-related emotional behaviours. Animal models of early-life adversity, in particular, maternal separation (MS) in rodents, demonstrate lasting deleterious effects on both the gut and the brain. Here, we review the effects of MS on both systems with a focus on stress-related behaviours. In addition, we discuss more recent findings showing the impact of gut-directed interventions, including nutrition with pre- and probiotics, illustrating the role played by gut microbiota in mediating the long-term effects of MS. Overall, preclinical studies suggest that nutritional approaches with pro- and prebiotics may constitute safe and efficient strategies to attenuate the effects of early-life stress on the gut–brain axis. Further research is required to understand the complex mechanisms underlying gut–brain interaction dysfunctions after early-life stress as well as to determine the beneficial impact of gut-directed strategies in a context of early-life adversity in human subjects.

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