Social isolation rearing-induced impairment of the hippocampal neurogenesis is associated with deficits in spatial memory and emotion-related behaviors in juvenile mice

J Neurochem. 2008 May;105(3):921-32. doi: 10.1111/j.1471-4159.2007.05207.x. Epub 2007 Dec 24.


Experiences during brain development may influence the pathogenesis of developmental disorders. Thus, social isolation (SI) rearing after weaning is a useful animal model for studying the pathological mechanisms of such psychiatric diseases. In this study, we examined the effect of SI on neurogenesis in the hippocampal dentate gyrus (DG) relating to memory and emotion-related behaviors. When newly divided cells were labeled with 5-bromo-2'-deoxyuridine (BrdU) before SI, the number of BrdU-positive cells and the rate of differentiation into neurons were significantly decreased after 4-week SI compared with those in group-housed mice. Repeated treatment of fluoxetine prevented the SI-induced impairment of survival of newly divided cells and ameliorated spatial memory impairment and part of aggression in SI mice. Furthermore, we investigated the changes in gene expression in the DG of SI mice by using DNA microarray and real-time PCR. We finally found that SI reduced the expression of development-related genes Nurr1 and Npas4. These findings suggest that communication in juvenile is important in the survival and differentiation of newly divided cells, which may be associated with memory and aggression, and raise the possibility that the reduced expression of Nurr1 and/or Npas4 may contribute to the impairment of neurogenesis and memory and aggression induced by SI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Behavior, Animal / physiology
  • Bromodeoxyuridine
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dentate Gyrus / growth & development
  • Dentate Gyrus / physiopathology
  • Emotions / physiology
  • Fluoxetine / pharmacology
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / genetics
  • Hippocampus / growth & development*
  • Hippocampus / physiopathology*
  • Male
  • Memory Disorders / genetics
  • Memory Disorders / physiopathology*
  • Mental Disorders / genetics
  • Mental Disorders / physiopathology*
  • Mice
  • Mice, Inbred ICR
  • Neuronal Plasticity / genetics*
  • Neurons / physiology
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Social Behavior
  • Social Isolation / psychology*
  • Stem Cells / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Npas4 protein, rat
  • Nr4a2 protein, mouse
  • Nr4a2 protein, rat
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Serotonin Uptake Inhibitors
  • Transcription Factors
  • Fluoxetine
  • Bromodeoxyuridine