Journal
JOURNAL OF NEUROCHEMISTRY
Volume 135, Issue 5, Pages 975-986Publisher
WILEY
DOI: 10.1111/jnc.13347
Keywords
corticotropin-releasing hormone; glucocorticoid receptor; locus coeruleus; neuropeptide Y; post-traumatic stress disorder; tyrosine hydroxylase
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Funding
- US Army, Department of Defense Medical Research and Development Program [DM102281]
- CDMRP [DM102281, 545735] Funding Source: Federal RePORTER
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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 (SPSN). Seven days later, TH protein, but not mRNA, was elevated in LC only of the SPSN group. Although 90% of TH positive cells expressed GR, its levels were unaltered. Compared to unstressed controls, LC of SPSN, 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.
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