Hippocampal over-expression of cyclooxygenase-2 (COX-2) is associated with susceptibility to stress-induced anhedonia in mice
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-284056
- The phenomenon of individual variability in susceptibility/resilience to stress and depression, in which the hippocampus plays a pivotal role, is attracting increasing attention. We investigated the potential role of hippocampal cyclooxygenase-2 (COX-2), which regulates plasticity, neuroimmune function, and stress responses that are all linked to this risk dichotomy. We used a four-week-long chronic mild stress (CMS) paradigm, in which mice could be stratified according to their susceptibility/resilience to anhedonia, a key feature ofThe phenomenon of individual variability in susceptibility/resilience to stress and depression, in which the hippocampus plays a pivotal role, is attracting increasing attention. We investigated the potential role of hippocampal cyclooxygenase-2 (COX-2), which regulates plasticity, neuroimmune function, and stress responses that are all linked to this risk dichotomy. We used a four-week-long chronic mild stress (CMS) paradigm, in which mice could be stratified according to their susceptibility/resilience to anhedonia, a key feature of depression, to investigate hippocampal expression of COX-2, a marker of microglial activation Iba-1, and the proliferation marker Ki67. Rat exposure, social defeat, restraints, and tail suspension were used as stressors. We compared the effects of treatment with either the selective COX-2 inhibitor celecoxib (30 mg/kg/day) or citalopram (15 mg/kg/day). For the celecoxib and vehicle-treated mice, the Porsolt test was used. Anhedonic (susceptible) but not non-anhedonic (resilient) animals exhibited elevated COX-2 mRNA levels, increased numbers of COX-2 and Iba-1-positive cells in the dentate gyrus and the CA1 area, and decreased numbers of Ki67-positive cells in the subgranular zone of the hippocampus. Drug treatment decreased the percentage of anhedonic mice, normalized swimming activity, reduced behavioral despair, and improved conditioned fear memory. Hippocampal over-expression of COX-2 is associated with susceptibility to stress-induced anhedonia, and its pharmacological inhibition with celecoxib has antidepressant effects that are similar in size to those of citalopram.…
Autor(en): | Tatyana Strekalova, Dmitrii Pavlov, Alexander Trofimov, Daniel C. Anthony, Andrei Svistunov, Andrey Proshin, Aleksei Umriukhin, Alexei Lyundup, Klaus-Peter Lesch, Raymond Cespuglio |
---|---|
URN: | urn:nbn:de:bvb:20-opus-284056 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Lehrstuhl für Molekulare Psychiatrie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Erscheinungsjahr: | 2022 |
Band / Jahrgang: | 23 |
Heft / Ausgabe: | 4 |
Aufsatznummer: | 2061 |
Originalveröffentlichung / Quelle: | International Journal of Molecular Sciences (2022) 23:4, 2061. https://doi.org/10.3390/ijms23042061 |
DOI: | https://doi.org/10.3390/ijms23042061 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | anhedonia; celecoxib; chronic stress; citalopram; fear conditioning; hippocampus; inducible cyclooxygenase-2 (COX-2); major depression; mouse; stress resilience |
Datum der Freischaltung: | 24.07.2023 |
Datum der Erstveröffentlichung: | 13.02.2022 |
EU-Projektnummer / Contract (GA) number: | 101007642 |
EU-Projektnummer / Contract (GA) number: | 728018 |
OpenAIRE: | OpenAIRE |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |