Lasting downregulation of the lipid peroxidation enzymes in the prefrontal cortex of mice susceptible to stress-induced anhedonia.
Antioxidant enzymes and lipid peroxidation in the brain are involved in neuropsychiatric pathologies, including depression. 14- or 28-day chronic stress model induced a depressive syndrome defined by lowered reward sensitivity in C57BL/6J mice and changed gene expression of peroxidation enzymes as shown in microarray assays. We studied how susceptibility or resilience to anhedonia is related to lipid peroxidation in the prefrontal cortex (PFC). With 14-day stress, a comparison of the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX) and accumulation of malondialdehyde (MDA) revealed a decrease of the first two measures in susceptible, but not in resilient animals or in stressed mice chronically dosed with imipramine (7mg/kg/day). Acute stress elevated activity of CAT and SOD and dynamics of MDA accumulation in the PFC that was prevented by imipramine (30mg/kg). 28-day stress evoked anhedonia lasting two but not five weeks while behavioural invigoration was detected at the latter time point in anhedonic but not non-anhedonic mice; enhanced aggressive traits were observed in both groups. After two weeks of a stress-free period, CAT and SOD activity levels in the PFC were reduced in anhedonic animals; after five weeks, only CAT was diminished. Thus, in the present chronic stress depression paradigm, lasting alterations in brain peroxidation occur not only during anhedonia but also in the recovery period and are accompanied by behavioural abnormalities in mice. This mimics behavioural and neurochemical deficits observed in depressed patients during remission which could be used to develop remedies preventing their relapse.
CNRS, UMR6265, CSGA, 9E boulevard Jeanne d'Arc, 21000 Dijon, France; INRA, UMR1324, CSGA, 9E boulevard Jeanne d'Arc, 21000 Dijon, France; Université de Bourgogne, CSGA, 9E boulevard Jeanne d'Arc, 21000 Dijon, France; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal.
Brandon H
BH
Cline
Department of Pharmacology, Oxford University, Mansfield Road, OX1 3QT Oxford, UK; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal.
Daniel C
DC
Anthony
Institute of General Pathology and Pathophysiology, Baltyiskaia 8, 125315 Moscow, Russia; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal.
Alexander
A
Lysko
Institute of Normal Physiology, Baltyiskaia 8, 125315 Moscow, Russia; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal.
Oleg
O
Dolgov
Institute of Normal Physiology, Baltyiskaia 8, 125315 Moscow, Russia; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal.
Konstantin
K
Anokhin
Maastricht Medical Centre in Annadal, Department of Preventive Medicine, Becanusstraat 17 A0, 6216 BX Maastricht, Netherlands; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal.
Careen
C
Schroeter
Institute of General Pathology and Pathophysiology, Baltyiskaia 8, 125315 Moscow, Russia; University of Wisconsin, Carbon Cancer Centre, WIMR 3016, 1111 Highland Avenue, Madison, WI 53705, USA; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal.
Dmitry
D
Malin
Institute of General Pathology and Pathophysiology, Baltyiskaia 8, 125315 Moscow, Russia; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal.
Aslan
A
Kubatiev
Department of Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229 ER Maastricht, Netherlands; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal.
Harry W
HW
Steinbusch
Department of Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229 ER Maastricht, Netherlands; Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Germany; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal.
Klaus-Peter
KP
Lesch
Maastricht Medical Centre in Annadal, Department of Preventive Medicine, Becanusstraat 17 A0, 6216 BX Maastricht, Netherlands; Department of Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229 ER Maastricht, Netherlands; Institute of Physiologically Active Compounds RAS, Severnii proesd 1, 142100 Chernogolovka, Moscow Region, Russia; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal. Electronic address: t.strekalova@maastrichtuniversity.nl.
Tatyana
T
Strekalova
D000374:Aggression / Q000187:drug effects; D059445:Anhedonia / Q000187:drug effects; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005518:Food Preferences; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000201:enzymology*; D055500:Resilience, Psychological; D013315:Stress, Psychological / Q000201:enzymology* / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D007099:Imipramine
Anhedonia; Chronic stress depression model; Imipramine; Lipid peroxidation; Microarray; Prefrontal cortex