Cognitive deficit in hippocampal-dependent tasks in Werner syndrome mouse model
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Updated: Mar 8, 2026
Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
Published on: May 12, 2015
Khaoula Rekik1, Bernard Francés1, Philippe Valet2
1Université de Toulouse, France; Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), CNRS, UPS,118 route de Narbonne, F-31062 Toulouse, Cedex 9, France.
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.
Insights
Werner syndrome (WS) mice, a model for accelerated aging, show long-term memory impairment by 8 months old. This suggests premature aging impacts cognitive functions, particularly hippocampus-dependent memory.
Area of Science:
- Gerontology
- Neuroscience
- Molecular Biology
Background:
- Mammalian aging involves metabolic issues, cognitive decline, and DNA repair deficits.
- DNA repair alterations accelerate aging; unrepaired DNA damage in neurons can cause brain disorders.
- Werner syndrome (WS) mice, modeling accelerated aging, possess defects in DNA repair enzymes.
Purpose of the Study:
- To investigate the impact of Werner syndrome on learning and memory in a mouse model.
- To assess hippocampus-dependent and non-hippocampus-dependent memory in WS mice at different ages.
- To determine if WS mice exhibit cognitive aging phenotypes.
Main Methods:
- WS mice of 3, 5, and 8 months old were used.
- Behavioral paradigms included spatial object location, Morris water maze, fear conditioning, and object recognition.
- Locomotion and anxiety levels were monitored.
Main Results:
- No significant differences in locomotion or anxiety were observed in adult WS mice.
- Eight-month-old WS mice demonstrated long-term memory impairment.
- This impairment was comparable to that seen in naturally aged mice.
Conclusions:
- Adult WS mice exhibit aspects of cognitive aging, specifically long-term memory deficits.
- The study highlights the link between DNA repair deficiency and cognitive aging.
- WS mice serve as a valuable model for studying accelerated cognitive aging.
