Prognostic and Symptomatic Aspects of Rapid Eye Movement Sleep in a Mouse Model of Posttraumatic Stress Disorder

Abstract

Not every individual develops Posttraumatic Stress Disorder (PTSD) after the exposure to a potentially traumatic event. Therefore, the identification of pre-existing risk factors and early diagnostic biomarkers is of high medical relevance. However, no objective biomarker has yet progressed into clinical practice. Sleep disturbances represent commonly reported complaints in PTSD patients. In particular, changes in rapid eye movement sleep (REMS) properties are frequently observed in PTSD patients. Here, we examined in a mouse model of PTSD whether (1) mice developed REMS alterations after trauma and (2) whether REMS architecture before and/or shortly after trauma predicted the development of PTSD-like symptoms. We monitored sleep-wake behavior via combined electroencephalogram/electromyogram recordings immediately before (24 h pre), immediately after (0-48 h post) and 2 months after exposure to an electric foot shock in male C57BL/6N mice (n = 15). PTSD-like symptoms, including hyperarousal, contextual, and generalized fear, were assessed 1 month post-trauma. Shocked mice showed early onset and sustained elevation of REMS compared to non-shocked controls. In addition, REMS architecture before trauma was correlated with the intensity of acoustic startle responses, but not contextual fear, 1 month after trauma. Our data suggest REMS as prognostic (pre-trauma) and symptomatic (post-trauma) marker of PTSD-like symptoms in mice. Translated to the situation in humans, REMS may constitute a viable, objective, and non-invasive biomarker in PTSD and other trauma-related psychiatric disorders, which could guide pharmacological interventions in humans at high risk.

A Systems Approach Identifies Networks and Genes Linking Sleep and Stress: Implications for Neuropsychiatric Disorders

“…In addition, many known interactions between distinct aspects of stress and sleep biology were observed. This includes well-known physiological relationships, such as body weight measurements and plasma glucose levels (Figure 2C and G), as well as previously reported associations between sleep and stress traits, such as conditioned fear and REM sleep (Figure 2B and F) (Menz et al, 2013; Polta et al, 2013). Other phenotypic relationships were also observed.…”

Distinct Parameters in the EEG of the PLP α-SYN Mouse Model for Multiple System Atrophy Reinforce Face Validity

“…The general sleep/wake behavior of our young control animals (Figures 1, 2) is in accordance with previous findings in the literature on WAKE, NREMS, and REMS distribution in C57BL/6J mice (Tobler et al, 1997) and in C57BL/6N mice (Polta et al, 2013). Our old control mice expressed increased amounts of NREMS at the beginning of the active period, when compared to the young animals of the same group.…”

“…All recording electrodes, consisting of gold wire (diameter: 150 μm, Häfner, München, Germany) with ball-shaped endings were soldered to a PCP socket board (Type 861-87-008-10-001101, preci-dip, Switzerland), which was later connected to the pre-amplifier and the recording cable. For a detailed description of the surgical procedure and electrode design, please refer to Fulda et al (2011) and Polta et al (2013). During and after surgery, animals received analgesic treatment (Meloxicam, 0.5 mg/ml suspension, s.c. injection and 5 × 10 −4 mg/ml for 7 days in drinking water).…”

Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and Biological Phenotypes, and Future Challenges in Improving Translation

“…There is some early evidence that individual differences in immune response (74) predict trauma response in the SDS model. Furthermore, another study demonstrated that low hippocampal levels of N-acetylaspartate assessed by proton magnetic resonance spectroscopy and differences in pre-trauma REM predicted persistent susceptibility to inescapable shocks in mice (17; 88).…”

“…Susceptible and resilient animals have been defined by success or failure to escape subsequent shock exposures (16). Interestingly, REM immediately before (24 hrs) foot-shock exposure predicts long-term emergence of hyperarousal after the foot-shock protocol (17), suggesting that this paradigm may be useful in examining treatments. This paradigm also induces enhanced neuronal activity in the PFC and amygdala and decreased volume in the hippocampus (13; 18–23) (Table 2).…”