Chronic high dose of captopril induces depressive-like behaviors in mice: Possible mechanism of regulatory T cell in depression

Hyun Sun Park, Arum Han, Hye Lim Yeo, Min Jung Park, Min Jung You, Hyun Jin Choi, Chang Won Hong, Sang Hyuk Lee, Seung Hyun Kim, Borah Kim, Min Soo Kwon

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Major depression has various types of symptoms and disease courses with inconsistent response to monoamine-related antidepressants. Thus, monoamine theory may not be the only pathophysiologic pathway relevant to depression. Recently, it has been suggested that regulatory T cell (Treg) is associated with depression. Based on our previous study that showed decreased regulatory T cell (Treg) population following chronic high-dose captopril (CHC, 40 mg/kg/day 21 days) administration, we examined whether CHC alone can induce depressive-like behaviors in mice even without stressful stimuli. In this study, we found that CHC induced depressive-like behaviors in tail suspension test (TST) and forced swimming test (FST) without systemic illness, while it did not induce anhedonic behavior, anxiety-like behaviors, or sociality-related behavior. The depressive-like behaviors were rescued by either CHC washout or antidepressant. CHC caused reduction in foxp3 and gata3 mRNA expression in the lymph nodes with elevation in plasma IL-1β and IL-6. Interestingly, CHC increased serum angiotensin II level. In the hippocampus, CHC increased TNF-α and IL-6 mRNA expression with microglia activation while reduced glucocorticoid receptor expression. However, CHC did not affect to hippocampal kynurenine pathway, serotonin level, hypothalamic corticotropin-releasing hormone mRNA level, or serum corticosterone level. Consequently, we propose that CHC may induce a specific form of depressive-like behaviors via Treg reduction and microglial activation.

Original languageEnglish
Pages (from-to)72528-72543
Number of pages16
JournalOncotarget
Volume8
Issue number42
DOIs
StatePublished - 3 Aug 2017

Keywords

  • Angiotensin II
  • Captopril
  • cytokines
  • Depression
  • Regulatory T cell

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