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

Autor: Tatyana Strekalova, Dmitrii Pavlov, Alexander Trofimov, Daniel C. Anthony, Andrei Svistunov, Andrey Proshin, Aleksei Umriukhin, Alexei Lyundup, Klaus-Peter Lesch, Raymond Cespuglio
Přispěvatelé: Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience
Rok vydání: 2021
Předmět:
Male
Anhedonia
Wistar
PREFRONTAL CORTEX
Inbred C57BL
stress resilience
UP-REGULATION
Hindlimb Suspension/physiology
Hippocampus
DOUBLE-BLIND
Mice
Depression/drug therapy
Cyclooxygenase 2/metabolism
inducible cyclooxygenase-2 (COX-2)
Spectroscopy
Depression
INDUCIBLE CYCLOOXYGENASE
General Medicine
NONSTEROIDAL ANTIINFLAMMATORY DRUGS
Antidepressive Agents
Computer Science Applications
ANIMAL-MODELS
Hindlimb Suspension
INHIBITOR CELECOXIB
DEPRESSIVE SYMPTOMS
Serotonin Uptake Inhibitors/pharmacology
MESSENGER-RNA
Selective Serotonin Reuptake Inhibitors
AMPA-RECEPTORS
Anhedonia/drug effects
Psychological/drug therapy
Citalopram
Stress
Catalysis
Inorganic Chemistry
Celecoxib/pharmacology
Stress
Psychological/drug therapy
major depression
hippocampus
anhedonia
chronic stress
fear conditioning
celecoxib
citalopram
mouse
Animals
ddc:610
Hippocampus/drug effects
Physical and Theoretical Chemistry
Rats
Wistar
Molecular Biology
Swimming
Organic Chemistry
Citalopram/pharmacology
Rats
Mice
Inbred C57BL
Antidepressive Agents/pharmacology
Celecoxib
Cyclooxygenase 2
Swimming/physiology
Stress
Psychological
Zdroj: International Journal of Molecular Sciences; Volume 23; Issue 4; Pages: 2061
International journal of molecular sciences, 23(4):2061. Multidisciplinary Digital Publishing Institute (MDPI)
ISSN: 1422-0067
1661-6596
Popis: 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 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.
Databáze: OpenAIRE
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