Cognitive deficit in hippocampal-dependent tasks in Werner syndrome mouse model

Behav Brain Res. 2017 Apr 14:323:68-77. doi: 10.1016/j.bbr.2017.01.034. Epub 2017 Jan 21.


Mammalian aging is often characterized by metabolic disturbances, cognitive declines and DNA repairs deficiency, but the underlying molecular mechanisms are still not well understood. Alterations in DNA repair can significantly exacerbate aging. Mammalian neuronal cells which accumulate unrepaired DNA damage over time could potentially lead to brain functions disorders. Focusing on the ATP-dependent RecQ-type DNA helicase, an enzyme involved in repair of double strand DNA, a mouse model of Werner syndrome (WS) had been proposed as a model of accelerated aging. Until now, no study has investigated the impact of this premature aging syndrome on learning and memory. Spatial memory and cognitive flexibility are particularly affected by the aging process in both men and rodents. Studies have shown that aged mice exhibited similar performance than young adult mice on non-hippocampus dependent memory whereas their performances were decreased in hippocampus-dependent tasks. In this study, we have submitted 3, 5 and 8 month-old WS mice to several behavioral paradigms to evaluate hippocampus-dependent (spatial object location, Morris water maze and fear conditioning) and non hippocampus-dependent (object recognition) memories. No effect on the locomotion activity and anxiety level has been observed in adult WS mice. Interestingly, the 8 month-old WS mice exhibit long-term memory impairment similar to aged mice, suggesting that adult WS mice do develop some aspects of cognitive aging.

Keywords: Aging; Behavior; Memory; Mouse; Werner syndrome.

MeSH terms

  • Aging
  • Animals
  • Anxiety*
  • Behavior, Animal
  • Conditioning, Classical
  • Disease Models, Animal
  • Fear
  • Female
  • Hippocampus
  • Male
  • Maze Learning
  • Memory*
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity*
  • Recognition, Psychology
  • Werner Syndrome / psychology*
  • Werner Syndrome Helicase / genetics


  • Werner Syndrome Helicase
  • Wrn protein, mouse