Repeated Three-Hour Maternal Separation Induces Depression-Like Behavior and Affects the Expression of Hippocampal Plasticity-Related Proteins in C57BL/6N Mice.

Yaoyao Bian,Li Zeng,Guihua Xu,Lili Yang,Zhongli Wang,Qing Wang

doi:10.1155/2015/627837

Yaoyao Bian, Li Zeng + Show 4 more

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https://doi.org/10.1155/2015/627837

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Abstract

Adverse early life experiences can negatively affect behaviors later in life. Maternal separation (MS) has been extensively investigated in animal models in the adult phase of MS. The study aimed to explore the mechanism by which MS negatively affects C57BL/6N mice, especially the effects caused by MS in the early phase. Early life adversity especially can alter plasticity functions. To determine whether adverse early life experiences induce changes in plasticity in the brain hippocampus, we established an MS paradigm. In this research, the mice were treated with mild (15 min, MS15) or prolonged (180 min, MS180) maternal separation from postnatal day 2 to postnatal day 21. The mice underwent a forced swimming test, a tail suspension test, and an open field test, respectively. Afterward, the mice were sacrificed on postnatal day 31 to determine the effects of MS on early life stages. Results implied that MS induces depression-like behavior and the effects may be mediated partly by interfering with the hippocampal GSK-3β-CREB signaling pathway and by reducing the levels of some plasticity-related proteins.

Highlights

In mammals, adverse life events that occur in early neuronal development can change normal brain growth and stress vulnerability in adulthood [1]
A difference in weight was observed on PND14 (F2,27 = 4.07, P < 0.05), PND21 (F2,27 = 5.74, P < 0.01), and PND28 (F2,27 = 6.11, P < 0.01), where in MS180, the body weight were lighter than Control and MS15 since PND14 to PND28 (Table 1)
Our results showed that MS180 normalized the downregulated hippocampal mRNA and protein levels of brain-derived neurotrophic factor (BDNF); MS180 reduced the activation of CREB in the C57BL/6N mouse model

Summary

Introduction

Adverse life events that occur in early neuronal development can change normal brain growth and stress vulnerability in adulthood [1]. The time and duration of any stressful experience that occurs in the neonatal or adolescent period are possibly necessary to promote proper neuronal organization; these parameters can exacerbate the vulnerability to long-term behavioral changes [3]. Our study generally aimed to assess the mechanism by which the association between neonatal and adolescent stressful experiences may influence stress responsiveness and brain plasticity in C57BL/6N mice. Considering depression, researchers hypothesized that structural plasticity and neurotrophic factors are necessary to mediate behavioral responses to MS. In addition to NF-L, brain-derived neurotrophic factor (BDNF) is a key regulator of neuronal plasticity. The transcription of several genes, such as BDNF, is stimulated by activating the phosphorylation of cAMP response element-binding

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