Dataset Information

IL-4/10 prevents stress vulnerability following imipramine discontinuation.

ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusion

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.

SUBMITTER: Han A

PROVIDER: S-EPMC4628271 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Publications

IL-4/10 prevents stress vulnerability following imipramine discontinuation.

Han Arum A Yeo Hyelim H Park Min-Jung MJ Kim Seung Hyun SH Choi Hyun Jin HJ Hong Chang-Won CW Kwon Min-Soo MS

Journal of neuroinflammation 20151031

<h4>Background</h4>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.<h4>Me ...[more]

PMID: 26521132

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Project description:Administration of subanesthetic doses of ketamine during brain maturation represents a tool to mimic an early insult to the central nervous system (CNS). The cerebellum is a key player in psychosis pathogenesis, to which oxidative stress also contributes. Here, we investigated the impact of early celastrol administration on behavioral dysfunctions in adult mice that had received ketamine (30 mg/kg i.p.) at postnatal days (PNDs) 7, 9, and 11. Cerebellar levels of 8-hydroxydeoxyguanosine (8-OHdG), NADPH oxidase (NOX) 1 and NOX2, as well as of the calcium-binding protein parvalbumin (PV), were also assessed. Furthermore, celastrol effects on ketamine-induced alterations of proinflammatory (TNF-?, IL-6 and IL-1?) and anti-inflammatory (IL-10) cytokines in this brain region were evaluated. Early celastrol administration prevented ketamine-induced discrimination index decrease at adulthood. The same was found for locomotor activity elevations and increased close following and allogrooming, whereas no beneficial effects on sniffing impairment were detected. Ketamine increased 8-OHdG in the cerebellum of adult mice, which was also prevented by early celastrol injection. Cerebellar NOX1 levels were enhanced at adulthood following postnatal ketamine exposure. Celastrol per se induced NOX1 decrease in the cerebellum. This effect was more significant in animals that were early administered with ketamine. NOX2 levels did not change. Ketamine administration did not affect PV amount in the cerebellum. TNF-? levels were enhanced in ketamine-treated animals; however, this was not prevented by early celastrol administration. While no changes were observed for IL-6 and IL-1? levels, ketamine determined a reduction of cerebellar IL-10 expression, which was prevented by early celastrol treatment. Our results suggest that NOX inhibition during brain maturation prevents the development of psychotic-like behavioral dysfunctions, as well as the increased cerebellar oxidative stress and the reduction of IL-10 in the same brain region following ketamine exposure in postnatal life. This opens novel neuroprotective opportunities against early detrimental insults occurring during brain development.

Dataset Information

IL-4/10 prevents stress vulnerability following imipramine discontinuation.

Background

Methods

Results

Conclusion

Publications

IL-4/10 prevents stress vulnerability following imipramine discontinuation.

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