Maternal separation in rats induces neurobiological and behavioral changes on the maternal side

Ibrahim Bölükbas,Annakarina Mundorf,Nadja Freund

doi:10.1038/s41598-020-80087-6

Ibrahim Bölükbas, Annakarina Mundorf + Show 1 more

Open Access

https://doi.org/10.1038/s41598-020-80087-6

Copy DOI

Abstract

The time after parturition is a sensitive period for mothers where they are prone to develop psychopathological symptoms. Studies investigating dams after separation from their pups (maternal separation, MS) showed that MS induces alterations similar to postpartum depression. This study aims to give further details on affected behavior and neurobiology of dams after MS. MS in rats from postnatal day 2–20 over four hours daily was performed. Upon reunion, maternal behavior, and ultrasonic vocalization (USV) of dams were measured. On the day of weaning, dams were tested for anxiety-like behavior in the elevated-plus-maze and marble burying test. Then Morc1 mRNA in the medial prefrontal cortex and Nr3c1 encoding the glucocorticoid receptor mRNA in the hippocampus were measured using real-time PCR to examine possible neurobiological correlates in psychopathology and social behavior. GABA and glutamate serum levels were analyzed by high-performance liquid chromatography as peripheral markers for stress-induced psychopathology. MS in dams increased maternal care towards pups even though both groups show high levels of maternal behavior even in late lactation. Furthermore, the emission of 50-kHz and 22-kHz USVs increased significantly. No differences in anxiety-like behavior were detected. MS further reduced Morc1 but not Nr3c1 expression. Serum GABA but not glutamate levels were significantly increased in separated dams. This study reinforces the benefit of investigating dams after MS for studying postpartum stress. Subclinical markers mainly connected to depression, namely Morc1 and GABA, proved to be useful allowing for earlier detection of symptoms of critical postpartum stress.

Highlights

The time after parturition is a sensitive period for mothers where they are prone to develop psychopathological symptoms
While the chronic stress exposure in this sensitive phase of early development has been widely studied, it is often ignored that the postpartum phase is a vulnerable phase for dams or mothers making them prone to develop psychiatric disorders e.g. postpartum depression (PPD)[10]
A few studies have so far focused on consequences for the dams experiencing MS11,12. These studies mostly investigated influences of repeated maternal separation (MS) on maternal behavior measuring parameters such as time licking and nursing the pups or arched-back n ursing[13] and anxiety or depression-like behavior showing an increase of both, maternal care as well as anxiety and depression-like behavior after M S14

Summary

Introduction

The time after parturition is a sensitive period for mothers where they are prone to develop psychopathological symptoms. Abbreviations ANOVA Analysis of variance ELS Early life stress EPM Elevated-plus maze test FDR False discovery rate GABA Gamma-aminobutyric acid HPLC High-performance liquid chromatography mPFC Medial prefrontal cortex Morc[1] MORC family CW-type zinc finger 1 Nr3c1 Nuclear receptor subfamily 3 group C member 1 MS Maternal separation PD Postnatal day PPD Postpartum depression RT-PCR Real-time quantitative polymerase chain reaction USV Ultrasonic vocalizations. Studies investigating dams after MS have found lower Nr3c1 mRNA, encoding for the glucocorticoidreceptor, in the hippocampus and elevated plasma CORT levels confirming the chronic stress reaction induced by separation from the p ups[12] These studies found that imbalances in hormones and neurotransmitters are similar to those observed in humans suffering from PPD such as altered cortisol, prolactin levels, or differences in the serotonin-system[12,16,21]

Objectives

Methods

Results

Conclusion