Hippocampal Over-Expression of Cyclooxygenase-2 (COX-2) Is Associated with Susceptibility to Stress-Induced Anhedonia in Mice

The phenomenon of individual variability in susceptibility/resilience to stress and de-pression, 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 de-spair, 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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Авторы
Strekalova T. , Pavlov D. , Trofimov A. , Anthony D.C. , Svistunov A. , Proshin A. , Umriukhin A. , Lyundup A. , Lesch K.-P. , Cespuglio R.
Издательство
MDPI AG
Номер выпуска
4
Язык
Английский
Статус
Опубликовано
Номер
2061
Том
23
Год
2022
Организации
  • 1 Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, 6229 ER, Netherlands
  • 2 Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, Moscow, 119991, Russian Federation
  • 3 Hotchkiss Brain Institute, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, T2N 4N1, AB, Canada
  • 4 P.K. Anokhin Research Institute of Normal Physiology, Moscow, 125315, Russian Federation
  • 5 Research and Educational Resource Center for Cellular Technologies, Peoples’ Friendship, University of Russia, Moscow, 117198, Russian Federation
  • 6 Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Wuerzburg, 97080, Germany
  • 7 Centre de Recherche en Neurosciences de Lyon (CRNL), Bron, 69500, France
Ключевые слова
Anhedonia; Celecoxib; Chronic stress; Citalopram; Fear conditioning; Hippocampus; Inducible cyclooxygenase-2 (COX-2); Major depression; Mouse; Stress resilience
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