The Effect of Early Life Stress on Emotional Behaviors in GPR37KO Mice

GPR37 is an orphan G-protein-coupled receptor, a substrate of parkin which is linked to Parkinson’s disease (PD) and affective disorders. In this study, we sought to address the effects of early life stress (ELS) by employing the paradigm of limited nesting material on emotional behaviors in adult GPR37 knockout (KO) mice. Our results showed that, while there was an adverse effect of ELS on various domains of emotional behaviors in wild type (WT) mice in a sex specific manner (anxiety in females, depression and context-dependent fear memory in males), GPR37KO mice subjected to ELS exhibited less deteriorated emotional behaviors. GPR37KO female mice under ELS conditions displayed reduced anxiety compared to WT mice. This was paralleled by lower plasma corticosterone in GPR37KO females and a lower increase in P-T286-CaMKII by ELS in the amygdala. GPR37KO male mice, under ELS conditions, showed better retention of hippocampal-dependent emotional processing in the passive avoidance behavioral task. GPR37KO male mice showed increased immobility in the forced swim task and increased P-T286-CaMKII in the ventral hippocampus under baseline conditions. Taken together, our data showed overall long-term effects of ELS—deleterious or beneficial depending on the genotype, sex of the mice and the emotional context.

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Faculty Opinions recommendation of Early life stress accelerates behavioral and neural maturation of the hippocampus in male mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726338818.793536601 ◽

2017 ◽

Author(s):

Regina M Sullivan ◽

Maya Opendak

Keyword(s):

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Male Mice ◽

Neural Maturation

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Effects of early-life stress on peripheral and central mitochondria in male mice across ages

Psychoneuroendocrinology ◽

10.1016/j.psyneuen.2021.105346 ◽

2021 ◽

pp. 105346

Author(s):

S.R. Ruigrok ◽

K. Yim ◽

T.L. Emmerzaal ◽

B. Geenen ◽

N. Stöberl ◽

...

Keyword(s):

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Male Mice

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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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A Novel Mouse Model for Acute and Long-Lasting Consequences of Early Life Stress

Endocrinology ◽

10.1210/en.2008-0633 ◽

2008 ◽

Vol 149 (10) ◽

pp. 4892-4900 ◽

Cited By ~ 255

Author(s):

Courtney J. Rice ◽

Curt A. Sandman ◽

Mohammed R. Lenjavi ◽

Tallie Z. Baram

Keyword(s):

Mouse Model ◽

Paraventricular Nucleus ◽

Life Stress ◽

Early Life ◽

Molecular Mechanisms ◽

Early Life Stress ◽

Plasma Corticosterone ◽

Mrna Levels ◽

Dependent Manner ◽

Basal Plasma

Chronic early-life stress (ES) exerts profound acute and long-lasting effects on the hypothalamic-pituitary-adrenal system, with relevance to cognitive function and affective disorders. Our ability to determine the molecular mechanisms underlying these effects should benefit greatly from appropriate mouse models because these would enable use of powerful transgenic methods. Therefore, we have characterized a mouse model of chronic ES, which was provoked in mouse pups by abnormal, fragmented interactions with the dam. Dam-pup interaction was disrupted by limiting the nesting and bedding material in the cages, a manipulation that affected this parameter in a dose-dependent manner. At the end of their week-long rearing in the limited-nesting cages, mouse pups were stressed, as apparent from elevated basal plasma corticosterone levels. In addition, steady-state mRNA levels of CRH in the hypothalamic paraventricular nucleus of ES-experiencing pups were reduced, without significant change in mRNA levels of arginine vasopressin. Rearing mouse pups in this stress-provoking cage environment resulted in enduring effects: basal plasma corticosterone levels were still increased, and CRH mRNA levels in paraventricular nucleus remained reduced in adult ES mice, compared with those of controls. In addition, hippocampus-dependent learning and memory functions were impaired in 4- to 8-month-old ES mice. In summary, this novel, robust model of chronic early life stress in the mouse results in acute and enduring neuroendocrine and cognitive abnormalities. This model should facilitate the examination of the specific genes and molecules involved in the generation of this stress as well as in its consequences.

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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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