Single Prolonged Stress PTSD Model Triggers Progressive Severity of Anxiety, Altered Gene Expression in Locus Coeruleus and Hypothalamus and Effected Sensitivity to NPY
Biochemistry and Molecular Biology
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 microg/rat, but not 150 microg 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.
Serova, L., Nwokafor, C., Van Bockstaele, E., Reyes, B., Lin, X., & Sabban, E. (2019). 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, 29 (4), 482-492. https://doi.org/10.1016/j.euroneuro.2019.02.010