Filtern
Volltext vorhanden
- ja (6)
Gehört zur Bibliographie
- ja (6)
Dokumenttyp
Sprache
- Englisch (6)
Schlagworte
- mice (2)
- 5-HT receptors (1)
- Aggressive behaviour (1)
- Chronic stress (1)
- Cytokines (1)
- LPS (1)
- S-HT (1)
- SERT (1)
- Sert-deficient mice (1)
- Toll-like receptor 4 (TLR4) (1)
- Western diet (1)
- aging (1)
- anhedonia (1)
- attention-deficit/hyperactivity disorder (ADHD) (1)
- autism-like behavior (1)
- celecoxib (1)
- chronic stress (1)
- citalopram (1)
- diet (1)
- electroencephalogram (EEG) (1)
- fear conditioning (1)
- female aggression (1)
- glucose tolerance (1)
- glycogen synthase kinase-3 β (GSK-3β) (1)
- heterosis (1)
- hippocampus (1)
- inducible cyclooxygenase-2 (COX-2) (1)
- insulin receptor (IR) (1)
- lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5) (1)
- major depression (1)
- mouse (1)
- myelination (1)
- obesity (1)
- predation stress (1)
- serotonin receptors (1)
- sex differences (1)
- stress resilience (1)
- tryptophan hydroxylase-2 (Tph2) (1)
Institut
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.