The Role of Sleep in Mediating Post-Traumatic Stress Disorder
Abstract
This proposal addresses the Fiscal Year 2017 Peer Reviewed Medical Research Program topic area of “sleep disorders.” Specifically, the proposal will assess the role of sleep in mediating the negative consequences associated with post-traumatic stress disorder (PTSD). Sleep problems are common and can result in impaired cognitive and physical functioning. Left untreated, sleep problems can lead to many other mental and physical health conditions like depression, heart disease, or suicide. Of specific interest for this proposal is the role of sleep in the regulation of PTSD. Sleep disturbances are ubiquitous in PTSD and may be contributing to increased severity of PTSD symptoms. A detailed examination of the role of sleep in mediating the negative consequences of PTSD is required. It is the goal of this proposal to understand how sleep contributes the onset and maintenance of PTSD. PTSD is the result of experiencing a physical or psychological trauma and is common in military Veterans exposed to combat. Among the symptoms of PTSD, sleep disturbances including insomnia and nightmares are the most prevalent features and are rarely improved with the traditional methods of treating the disorder. Studying sleep in human PTSD patients is prohibitively difficult for many reasons. Given that trauma exposure is unpredictable, pre-trauma sleep is rarely if ever examined. Also, traumatizing humans in the laboratory would be unethical. We therefore propose to use a rat model of PTSD called single prolonged stress (SPS) that allows for sleep to be assessed and manipulated and trauma to be specifically timed. Using a rat model also permits invasive procedures for the examination of underlying behavioral and neurobiological changes. Rats exposed to SPS exhibit sleep and cognitive impairments similar to the human PTSD condition, which are easily measured using traditional methods. Assessing sleep problems related to trauma-exposure in this model will allow us to better understand the underlying neuro-physiology that we would be unable to examine in human populations. In Specific Aim 1, we will examine how sleep deprivation before trauma exposure impacts PTSD disease severity. In order to mimic real-world situations of sleep loss, we will perform both an acute sleep deprivation as well as a more prolonged 5-day sleep restriction protocol. We will sleep deprive outbred Long Evans rats for an acute 12 hours (1 time) or restrict their sleep to only 6 hours per day for 5 days (18 hours of total sleep deprivation per day) and then expose them to the SPS model. The animals will then perform a fear-associated memory task that will inform us how severe the PTSD phenotype is. We will compare the values on the fear-associated memory task to pre-trauma and post-trauma sleep values and identify sleep traits common among the most traumatized and the most resilient populations of animals. We hypothesize that sleep deprivation prior to SPS exposure will result in exaggerated PTSD phenotypes and that both the 5-day sleep restricted and the 1-day acutely deprived animals will both show fear-associated memory impairments. In Specific Aim 2, we will use optogenetics to improve sleep in traumatized animals. Optogenetics is a powerful tool that uses light to activate certain populations of cells in the alive and behaving animal. The optogenetic manipulation we are using results in increased levels of sleep. One group of animals will receive SPS without optogenetic stimulation to improve their sleep, while another group of animals will receive SPS with optogenetic improvement of sleep. After 7 days, these animals will be assessed for impairment on the fear-associated memory task. We hypothesize that improving sleep will result in improved functioning and better scores on the fear-associated memory task and will serve as a causal link between sleep and the cognitive impairment typically seen following trauma exposure. The princ
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810378
Entities
People
- William M Vanderheyden
Organizations
- United States Army
- Washington State University