TY  - JOUR
A1  - Strekalova, Tatyana
A1  - Pavlov, Dmitrii
A1  - Trofimov, Alexander
A1  - Anthony, Daniel C.
A1  - Svistunov, Andrei
A1  - Proshin, Andrey
A1  - Umriukhin, Aleksei
A1  - Lyundup, Alexei
A1  - Lesch, Klaus-Peter
A1  - Cespuglio, Raymond
T1  - Hippocampal over-expression of cyclooxygenase-2 (COX-2) is associated with susceptibility to stress-induced anhedonia in mice
JF  - International Journal of Molecular Sciences
N2  - 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.
KW  - major depression
KW  - inducible cyclooxygenase-2 (COX-2)
KW  - hippocampus
KW  - anhedonia
KW  - chronic stress
KW  - stress resilience
KW  - fear conditioning
KW  - celecoxib
KW  - citalopram
KW  - mouse
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284056
SN  - 1422-0067
VL  - 23
IS  - 4
ER  - 
TY  - JOUR
A1  - Petrasek, Tomas
A1  - Prokopova, Iva
A1  - Sladek, Martin
A1  - Weissova, Kamila
A1  - Vojtechova, Iveta
A1  - Bahnik, Stepan
A1  - Zemanova, Anna
A1  - Schönig, Kai
A1  - Berger, Stefan
A1  - Tews, Bjoern
A1  - Bartsch, Dusan
A1  - Schwab, Martin E.
A1  - Sumova, Alena
A1  - Stuchlik, Ales
T1  - Nogo-A-deficient transgenic rats show deficits in higher cognitive functions, decreased anxiety, and altered circadian activity patterns
JF  - Frontiers in Behavioral Neuroscience
N2  - Decreased levels of Nogo-A-dependent signaling have been shown to affect behavior and cognitive functions. In Nogo-A knockout and knockdown laboratory rodents, behavioral alterations were observed, possibly corresponding with human neuropsychiatric diseases of neurodevelopmental origin, particularly schizophrenia. This study offers further insight into behavioral manifestations of Nogo-A knockdown in laboratory rats, focusing on spatial and non-spatial cognition, anxiety levels, circadian rhythmicity, and activity patterns. Demonstrated is an impairment of cognitive functions and behavioral flexibility in a spatial active avoidance task, while non-spatial memory in a step-through avoidance task was spared. No signs of anhedonia, typical for schizophrenic patients, were observed in the animals. Some measures indicated lower anxiety levels in the Nogo-A-deficient group. Circadian rhythmicity in locomotor activity was preserved in the Nogo-A knockout rats and their circadian period (tau) did not differ from controls. However, daily activity patterns were slightly altered in the knockdown animals. We conclude that a reduction of Nogo-A levels induces changes in CNS development, manifested as subtle alterations in cognitive functions, emotionality, and activity patterns.
KW  - AAPA
KW  - circadian rhythmicity
KW  - passive avoidance
KW  - Nogo-A
KW  - anhedonia
KW  - neophobia
KW  - morris water maze
KW  - place avoidance task
KW  - neurite outgrowth inhibitor
KW  - axon regeneration
KW  - synaptic plasticity
KW  - down regulation
KW  - traumatic brain injury
KW  - carousel maze
KW  - messenger RNA
KW  - genetic deletion
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117073
VL  - 8
IS  - 90
ER  -