The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Maternal separation in mice leads to anxiety-like/aggressive behavior and increases immunoreactivity for glutamic acid decarboxylase and parvalbumin in the adolescence ventral hippocampus

  • Eu-Gene Kim (Department of Anatomy and Neuroscience, Eulji University School of Medicine) ;
  • Wonseok Chang (Department of Physiology and Biophysics, Eulji University School of Medicine) ;
  • SangYep Shin (Department of Physiology and Biophysics, Eulji University School of Medicine) ;
  • Anjana Silwal Adhikari (Department of Physiology and Biophysics, Eulji University School of Medicine) ;
  • Geun Hee Seol (Department of Basic Nursing Science, Korea University School of Nursing) ;
  • Dae-Yong Song (Department of Anatomy and Neuroscience, Eulji University School of Medicine) ;
  • Sun Seek Min (Department of Physiology and Biophysics, Eulji University School of Medicine)
  • Received : 2022.10.19
  • Accepted : 2022.10.31
  • Published : 2023.01.01
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Abstract

It has been reported that stressful events in early life influence behavior in adulthood and are associated with different psychiatric disorders, such as major depression, post-traumatic stress disorder, bipolar disorder, and anxiety disorder. Maternal separation (MS) is a representative animal model for reproducing childhood stress. It is used as an animal model for depression, and has well-known effects, such as increasing anxiety behavior and causing abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the effect of MS on anxiety or aggression-like behavior and the number of GABAergic neurons in the hippocampus. Mice were separated from their dams for four hours per day for 19 d from postnatal day two. Elevated plus maze (EPM) test, resident-intruder (RI) test, and counted glutamic acid decarboxylase 67 (GAD67) or parvalbumin (PV) positive cells in the hippocampus were executed using immunohistochemistry. The maternal segregation group exhibited increased anxiety and aggression in the EPM test and the RI test. GAD67-positive neurons were increased in the hippocampal regions we observed: dentate gyrus (DG), CA3, CA1, subiculum, presubiculum, and parasubiculum. PV-positive neurons were increased in the DG, CA3, presubiculum, and parasubiculum. Consistent with behavioral changes, corticosterone was increased in the MS group, suggesting that the behavioral changes induced by MS were expressed through the effect on the HPA axis. Altogether, MS alters anxiety and aggression levels, possibly through alteration of cytoarchitecture and output of the ventral hippocampus that induces the dysfunction of the HPA axis.

Keywords

Acknowledgement

Grant sponsor: Grant and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (NRF2021R1A2C1010951, 20151D1a1a01061326, 2019R1F1A1060276, 2021R1F1A1060027).

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