We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
IL-4/10 prevents stress vulnerability following imipramine discontinuation.
- Authors
Arum Han; Hyelim Yeo; Min-Jung Park; Seung Hyun Kim; Hyun Jin Choi; Chang-Won Hong; Min-Soo Kwon; Han, Arum; Yeo, Hyelim; Park, Min-Jung; Kim, Seung Hyun; Choi, Hyun Jin; Hong, Chang-Won; Kwon, Min-Soo
- Abstract
<bold>Background: </bold>Identifying stress vulnerability after antidepressant discontinuation may be useful in treating relapses in depression. Previous studies have suggested significant effects of the immune system as well as the central nervous system (CNS) on progression and induction of major depression. In the present study, we hypothesized that the factors that are not rescued by a tricyclic antidepressant imipramine may be associated with stress vulnerability and relapses in depression.<bold>Methods: </bold>To address this issue, mice were exposed to 2 h of restraint stress for 21 consecutive days (chronic restraint stress (CRS)) with or without co-treatment of imipramine. These groups were exposed to an electronic foot shock (FS) as additional stress after imipramine washout. Main targets of stress and antidepressants were analyzed in the hippocampus, lymph node, and serum after a series of depression-like behavior analysis.<bold>Results: </bold>In this study, we found for the first time that mice exposed to CRS with a tricyclic antidepressant imipramine co-treatment, which did not show depressive-like behaviors, were vulnerable to subsequent stressful stimuli compared to the non-stressed mice after imipramine washout. CRS mice with imipramine co-treatment did not show any difference in BDNF, serotonin receptors, pro-inflammatory cytokines, or kynurenine pathway in the hippocampus compared to the controls. However, peripheral IL-4, IL-10, and alternatively activated microglial phenotypes in the hippocampus were not restored with sustained reduction in CRS mice despite chronic imipramine administration. Supplementing recombinant IL-4 and IL-10 in co-Imi+CRS mice prevented the stress vulnerability on additional stress and restored factors related to alternatively activated microglia (M2) in the hippocampus.<bold>Conclusion: </bold>Thus, our results suggest that the reduced IL-4 and IL-10 levels in serum with hippocampal M2 markers may be involved in the stress vulnerability after imipramine discontinuation, and the restoration and modulation of these factors may be useful to some forms of depression-associated conditions.
- Subjects
INTERLEUKINS; IMIPRAMINE; PREVENTION of psychological stress; PSYCHOLOGICAL vulnerability; ANTIDEPRESSANTS; MENTAL depression; RECOMBINANT proteins; ANXIETY; ANIMAL behavior; ANIMAL experimentation; BEHAVIOR; CELLS; ELECTROCONVULSIVE therapy; DRUG withdrawal symptoms; FOOD preferences; HIPPOCAMPUS (Brain); LYMPH nodes; MICE; RESTRAINT of patients; PSYCHOLOGICAL stress; PSYCHOLOGICAL factors; PSYCHOLOGY; THERAPEUTICS
- Publication
Journal of Neuroinflammation, 2015, Vol 12, p1
- ISSN
1742-2094
- Publication type
journal article
- DOI
10.1186/s12974-015-0416-3