Molecular and Anatomical Effects of Circadian Disruption on the Stress Axis
Abstract
ABSTRACT This project will explore the neurobiological consequences of the circadian rhythm that may result in long-term alterations in neuroendocrine responses to stress. The proper regulation of the hypothalamic-pituitary-adrenal (HPA) axis is important for optimum physiological function and survivability of an individual (Handa and Weiser, 2014; Myers et al., 2014). Not only does the HPA axis control hormonal responses to stress, but its activity also synchronizes physiological systems with environmental cues and rhythms. When the HPA axis does not function appropriately and circulating glucocorticoid levels are inappropriate in amplitude or timing, the development of numerous physiological and psychological disorders is facilitated. These include metabolic disruption, cardiovascular disease, immunological variations, sleep/wake inefficiencies (including reduced performance in operational environments), neuropsychiatric disease, neurodegenerative diseases and putative increased cancer risks. These are all areas of significant concern within the Naval and the broader Department of Defense community particularly during training and deployment. To date, the relationship between changes in circadian rhythms and the stress axis is unknown with little understanding of how sex may impact the interaction. To fill this gap, these studies will explore sex differences in responses to different light cycles using transgenic mouse models with particular emphasis on regulation of HPA axis. Aim 1 will determine the effect of short- (1 week) and long-term (4 weeks) circadian disruption on the expression of genes relevant to CRH neuronal function. This aim will focus on how the circadian environment will alter gene expression in CRH neurons. Aim 2 will determine whether circadian disruption alters the stress-induced activation of CRH neurons in the PVN and in neurons of the limbic system that control CRH neuronal function. Aim 3 will determine if circadian disruption causes morphological changes in limbic system neurons that project to the PVN. Collectively, these studies will address the gap of how circadian disruption may alter CRH neuronal function in a sex dependent manner.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 22, 2016
- Source ID
- N000141512305
Entities
People
- Tao-yiao Wu
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- Office of Naval Research
- United States Navy