Locus coeruleus response to single‐prolonged stress and early intervention with intranasal neuropeptide Y
Abstract
Dysregulation of the central noradrenergic system is a core feature of post‐traumatic stress disorder (PTSD). Here, we examined molecular changes in locus coeruleus (LC) triggered by single‐prolonged stress (SPS) PTSD model at a time when behavioral symptoms are manifested, and the effect of early intervention with intranasal neuropeptide Y (NPY). Immediately following SPS stressors, male SD rats were administered intranasal NPY (SPS/NPY) or vehicle (SPS/V). Seven days later, TH protein, but not mRNA, was elevated in LC only of the SPS/V group. Although 90% of TH positive cells expressed GR, its levels were unaltered. Compared to unstressed controls, LC of SPS/V, but not SPS/NPY, expressed less Y2 receptor mRNA with more CRHR1 mRNA in subset of animals, and elevated corticotropin‐releasing hormone (CRH) in central nucleus of amygdala. Following testing for anxiety on elevated plus maze (EPM), there were significantly increased TH, DBH and NPY mRNAs in LC of SPS‐treated, but not previously unstressed animals. Their levels highly correlated with each other but not with behavioral features on EPM. Thus, SPS triggers long‐term noradrenergic activation and higher sensitivity to mild stressors, perhaps mediated by the up‐regulation influence of amygdalar CRH input and down‐regulation of Y2R presynaptic inhibition in LC. Results also demonstrate the therapeutic potential of early intervention with intranasal NPY for traumatic stress‐elicited noradrenergic impairments.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 30, 2015
- Source ID
- 10.1111/jnc.13347
Entities
People
- Emelie Olsson
- Esther L Sabban
- Lidia Serova
- Lishay G. Alaluf
- Marcela Laukova
Organizations
- New York Medical College
- Sahlgrenska University Hospital
- Slovak Academy of Sciences
- United States Department of Defense