rhythmicity in mice selected for extremes in stress reactivity behavioural, endocrine and sleep changes resembling endophenotypes of major depression韵律性小鼠选择极端的压力反应行为,内分泌和睡眠变化类似表型的抑郁症.pdfVIP

Rhythmicity in Mice Selected for Extremes in Stress Reactivity: Behavioural, Endocrine and Sleep Changes Resembling Endophenotypes of Major Depression 1. 1. ¨ 1 2 1 1 Chadi Touma *, Thomas Fenzl , Jorg Ruschel , Rupert Palme , Florian Holsboer , Mayumi Kimura , Rainer Landgraf1 1 Max Planck Institute of Psychiatry, Munich, Germany, 2 Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria Abstract Background: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including hyper- or hypo-activity of the stress hormone system, plays a critical role in the pathophysiology of mood disorders such as major depression (MD). Further biological hallmarks of MD are disturbances in circadian rhythms and sleep architecture. Applying a translational approach, an animal model has recently been developed, focusing on the deviation in sensitivity to stressful encounters. This so-called ‘stress reactivity’ (SR) mouse model consists of three separate breeding lines selected for either high (HR), intermediate (IR), or low (LR) corticosterone increase in response to stressors. Methodology/Principle Findings: In order to contribute to the validation of the SR mouse model, our study combined the analysis of behavioural and HPA axis rhythmicity with sleep-EEG recordings in the HR/IR/LR mouse lines. We found that hyper-responsiveness to stressors was associated with psychomotor alterations (increased locomotor activity and exploration towards the end of the resting period), resembling symptoms like restlessness, sleep continuity disturbances and early awakenings that are commonly observed in melancholic depression. Additionally, HR mice