Chevalier, Celeste M. and Krampert, Luka and Schreckenbach, Monika and Schubert, Christine F. and Reich, Johanna and Novak, Bozidar and Schmidt, Mathias and Rutten, Bart P. F. and Schmidt, Ulrike (2021) MMP9 mRNA is a potential diagnostic and treatment monitoring marker for PTSD: Evidence from mice and humans. EUROPEAN NEUROPSYCHOPHARMACOLOGY, 51. pp. 20-32. ISSN 0924-977X, 1873-7862
Full text not available from this repository. (Request a copy)Abstract
Although matrix metalloproteinase 9 (MMP9) has been found associated with various psychiatric disorders and with threat memories in humans, its role in post-traumatic stress disorder (PTSD) and related animal models is understudied. Thus, we analyzed MMP9 mRNA expression kinetics during two different stress experiments, i.e., the Trier Social Stress Test and the dexamethasone suppression test (DST), in whole blood of two independent cohorts of PTSD patients vs. non-traumatized healthy controls (HC) and, moreover, in a mouse model of PTSD and in dexamethasone-treated mice. Besides MMP9, we quantified mRNA levels of four of its regulators, i.e., interleukin (IL)-1 receptor 1 and 2 (IL1R1, IL1R2), IL-6 receptor and tumor necrosis factor receptor 1 (TNFR1) in 10 patients exposed to the DST before vs. after successful PTSD psychotherapy vs. 13 HC and, except from Il6r, also in different brain regions of the PTSD mouse model. We are the first to show that blood MMP9 mRNA concentrations were elevated after acute dexamethasone in PTSD patients, improved upon partial remission of PTSD and were, furthermore, also elevated, together with its regulator Tnfr1, in the prefrontal cortex of PTSDlike mice. In contrast, blood TNFR1 and IL1R2 were markedly underexpressed in PTSD patients. In conclusion, we found translational evidence supporting that, I, TNFR1 and MMP9 mRNA expression might be involved in PTSD pathobiology, II, might constitute potential diagnostic blood biomarkers for PTSD and, importantly, III, post-dexamethasone blood MMP9 hyperexpression, which speculatively results from post-dexamethasone underexpression of IL1R2, might serve also as potential treatment monitoring biomarker for PTSD. (c) 2021 Elsevier B.V. and ECNP. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POSTTRAUMATIC-STRESS-DISORDER; SERUM CONCENTRATIONS; PERIPHERAL-BLOOD; GENE-EXPRESSION; TNF-ALPHA; MATRIX-METALLOPROTEINASE-9; MOUSE; DEXAMETHASONE; BIOMARKERS; GLUCOCORTICOIDS; Post-traumatic stress disorder; Trier Social Stress Test (TSST); Dexamethasone suppression test; Mouse model of PTSD; PTSD biomarkers; exposure therapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Sep 2022 12:57 |
| Last Modified: | 27 Sep 2022 12:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48086 |
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