Journal article
Single prolonged stress PTSD model triggers progressive severity of anxiety, altered gene expression in locus coeruleus and hypothalamus and effected sensitivity to NPY
European neuropsychopharmacology, v 29(4), pp 482-492
01 Apr 2019
PMID: 30878321
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
PTSD is heterogeneous disorder that can be long lasting and often has delayed onset following exposure to a traumatic event. Therefore, it is important to take a staging approach to evaluate progression of biological mechanisms of the disease. Here, we begin to evaluate the temporal trajectory of changes following exposure to traumatic stressors in the SPS rat PTSD model. The percent of animals displaying severe anxiety on EPM increased from 17.5% at one week to 57.1% two weeks after SPS stressors, indicating delayed onset or progressive worsening of the symptoms. The LC displayed prolonged activation, and dysbalance of the CRH/NPY systems, with enhanced CRHR1 gene expression, coupled with reduced mRNAs for NPY and Y2R. In the mediobasal hypothalamus, increased CRH mRNA levels were sustained, but there was a flip in alterations of HPA regulatory molecules, GR and FKBP5 and Y5 receptor at two weeks compared to one week. Two weeks after SPS, intranasal NPY at 300 mu g/rat, but not 150 mu g which was effective after one week, reversed SPS triggered elevated anxiety. It also reversed SPS elicited depressive/despair symptoms and hyperarousal. Overall, the results reveal time-dependent progression in development of anxiety symptoms and molecular impairments in gene expression for CRH and NPY systems in LC and mediobasal hypothalamus by SPS. With longer time afterwards only a higher dose of NPY was effective in reversing behavioral impairments triggered by SPS, indicating that therapeutic approaches should be adjusted according to the degree of biological progression of the disorder. (C) 2019 Published by Elsevier
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Details
- Title
- Single prolonged stress PTSD model triggers progressive severity of anxiety, altered gene expression in locus coeruleus and hypothalamus and effected sensitivity to NPY
- Creators
- Lidia Serova - New York Medical CollegeChiso Nwokafor - New York Medical CollegeElisabeth J. Van Bockstaele - Drexel UniversityBeverly A. S. Reyes - Drexel UniversityXiaoping Lin - New York Medical CollegeEsther L. Sabban - New York Medical College
- Publication Details
- European neuropsychopharmacology, v 29(4), pp 482-492
- Publisher
- Elsevier
- Number of pages
- 11
- Grant note
- 49-506 / NYMC/Touro Bridge Funding Program DA09082 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA W81XWH-16-1-0016 / Office of the Assistant Secretary of Defense for Health Affairs through the U.S. Department of Defense (DOD) Department of Defense Broad Agency Announcement for Extramural Medical Research
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000465172300003
- Scopus ID
- 2-s2.0-85062805710
- Other Identifier
- 991019184821204721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Clinical Neurology
- Neurosciences
- Pharmacology & Pharmacy
- Psychiatry