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

Abstract
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.
AuthorsKhaoula Rekik, Bernard Francés, Philippe Valet, Cédric Dray, Cédrick Florian
JournalBehavioural brain research (Behav Brain Res) Vol. 323 Pg. 68-77 (04 14 2017) ISSN: 1872-7549 [Electronic] Netherlands
PMID28119126 (Publication Type: Journal Article)
CopyrightCopyright © 2017 Elsevier B.V. All rights reserved.
Chemical References
  • Werner Syndrome Helicase
  • Wrn protein, mouse
Topics
  • 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)

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