Research reportBehavioral effects of chronic stress in the Fmr1 mouse model for fragile X syndrome

- Behavioral sensitivity to stress was dramatically reduced in Fmr1-KO mice, the main animal model of Fragile X Syndrome.
- Repeated exposure to stress induced social and cognitive deficits only in WT mice.
- Chronic stress did not affect exploration, anxiety-like behaviors or corticosterone levels.
- The impact of stress depended on the type of stressors (restraint versus unpredictable stress) and the behavior tested.

Fragile X Syndrome (FXS) is a pervasive developmental disorder due to a mutation in the FMR1 X-linked gene. Despite its clear genetic cause, the expression of FXS symptoms is known to be modulated by environmental factors, including stress. Furthermore, several studies have shown disturbances in stress regulatory systems in FXS patients and Fmr1 mice. These studies have mostly focused on the hormonal responses to stress, using the acute exposure to a single type of stressor. Hence, little is known about the behavioral effects of stress in FXS, and the importance of the nature of the stressing procedure, especially in the context of a repeated exposure that more closely resembles real life conditions. Here we evaluated the effects of chronic exposure to different types of stress (i.e., either repeated restraint or unpredictable stress) on the behavioral phenotype of adult Fmr1 mice. Our results demonstrated that chronic stress induced deficits in social interaction and working memory only in WT mice and the impact of stress depended on the type of stressors and the specific behavior tested. Our data suggest that the behavioral sensitivity to stress is dramatically reduced in FXS, opening new views on the impact of gene-environment interactions in this pathology.