Hippocampal neurogenesis of Wistar Kyoto rats is congenitally impaired and correlated with stress resistance

Behav Brain Res. 2017 Jun 30;329:148-156. doi: 10.1016/j.bbr.2017.04.046. Epub 2017 Apr 30.


The hippocampus is thought to be an important region for depression. However, the relationship between hippocampal neurogenesis and depression is still controversial. Wistar Kyoto (WKY) rats are frequently used as a depression model. WKY rats are known to show physiologically abnormal features, and these features resemble abnormalities seen in depressed patients. However, the neurogenesis of WKY rats is still unknown. In this study, we first evaluated the neurogenesis of WKY rats and compared it to that of Wistar (WIS) rats. No strain effect was observed in the number of cells positive for 5-bromo-2'-deoxyuridine (BrdU) and BrdU/Doublecortin (Dcx) in the subventricular zone (SVZ). However, the number of BrdU- and BrdU/Dcx-positive cells in the dentate gyrus (DG) of the hippocampus was significantly lower in WKY rats than in WIS rats. Next, we evaluated the correlation between neurogenesis and behavior tests. Behavior tests did not affect neurogenesis in either strain. Hippocampal neurogenesis correlated negatively with the results of a forced swim test (FST) on day 2 in each strain. That is, rats with a lower level of native neurogenesis in the DG showed a higher level of learned helplessness induced by the inescapable stress of the FST on day 1. Our findings indicate that hippocampal neurogenesis in WKY rats is congenitally impaired in contrast to that in WIS rats. Native cell proliferation and neurogenesis in the DG are correlated with stress resistance. These findings may be useful for developing new targets for depression treatment.

Keywords: Depression; Forced swim test; Hippocampus; Neurogenesis; Stress; Wistar Kyoto rat.

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Count
  • Cell Proliferation
  • Depression / pathology*
  • Disease Models, Animal
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Exploratory Behavior / physiology
  • Hippocampus / physiopathology*
  • Lateral Ventricles / pathology
  • Lateral Ventricles / physiopathology
  • Microtubule-Associated Proteins / metabolism
  • Neurogenesis / physiology*
  • Neurons / pathology*
  • Neuropeptides / metabolism
  • Rats
  • Rats, Inbred WKY
  • Rats, Wistar
  • Statistics as Topic
  • Sucrose / administration & dosage
  • Swimming / psychology


  • Dcx protein, rat
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Sucrose
  • Bromodeoxyuridine