Emotional Impairments and Neuroinflammation are Induced in Male Mice Invulnerable to Repeated Social Defeat Stress. (1st September 2020)

• Record Type: Journal Article
• Authors: Ito, Naoki; Sasaki, Kazunori; Takemoto, Hiroaki; Kobayashi, Yoshinori; Isoda, Hiroko; Odaguchi, Hiroshi
• Is Part Of: Neuroscience. Volume 443(2020)
• Page Start: 148
• Page End: 163
• Publication Date: 2020-09-01
• Subjects: ACFC ambiguous-cue fear conditioning -- ANOVA analysis of variance -- ATP adenosine triphosphate -- CS conditioned stimuli -- DG dentate gyrus -- DMEM Dulbecco's modified Eagle's medium -- FST forced swim test -- GFAP glial fibrillary acidic protein -- Iba1 ionized calcium binding adaptor molecule 1 -- ICAM-1 intercellular adhesion molecule 1 -- LD light–dark -- LPS lipopolysaccharide -- Mino minocycline -- mRSDS modified version of repeated social defeat stress -- NCB negative cognitive bias -- NG2 polydendrocytes -- NPY neuropeptide Y -- PBS phosphate-buffered saline -- SEM standard error of the mean -- SI social interaction -- TNF-α tumor necrosis factor-α; social defeat stress -- negative cognitive bias -- depression -- neuroinflammation -- microglia; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.07.023
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Modified repeated social defeat stress (mRSDS) triggers negative cognitive bias and depression-like behaviors in BALB/c mice. Mice susceptible and resilient to mRSDS show distinct profiles in neuroinflammation and gene expression in the hippocampus. Mice resilient to mRSDS are no longer regarded as intact emotionally and neurobiologically. Minocycline reverses mRSDS-induced depression-like behaviors and neuroinflammation, but not negative cognitive bias. Anti-neuroinflammatory intervention does not necessarily alleviate the stress-induced behavioral deficits. Abstract: Prolonged stress triggers neuroinflammation, which plays a significant role in the development of depression; however, stressed people do not always suffer from depression because of individual differences in stress vulnerability. Negative cognitive bias (NCB) toward pessimistic judgment often underlies depressive episodes. However, a relationship between stress vulnerability, neuroinflammation, and NCB remains elusive. In addition, an animal model with all the traits would be a powerful tool for studying the etiology of depression and its therapeutic approaches. Accordingly, this study evaluated the effect of stress vulnerability on neuroinflammation and depression-related behaviors, including NCB in males, using a modified version of repeated social defeat stress (mRSDS) paradigm, a validated animal model of psychosocial stress. Exposure to mRSDS, consisting of 5 min of social defeat by unfamiliar CD-1 aggressor mice for five consecutive days, caused NCB, which co-occurred with depressive- and anxiety-like behaviors, and neuroinflammation in male BALB/c mice. Treatment with minocycline, an antibiotic with anti-inflammatory property, blocked mRSDS-induced depressive-like behaviors and neuroinflammation, but not NCB, indicating the limited effect of an anti-inflammatory intervention. In addition, marked differences were found in neuroinflammatory profiles and hippocampal gene expression patterns between resilient and unstressed mice, as well as between susceptible and resilient mice. Therefore, mice resilient to mRSDS are indeed not intact. Our findings provide insights into the unique features of the mRSDS model in male BALB/c mice, which could be used to investigate the etiological mechanisms underlying depression as well as bridge the gap in the relationship between stress vulnerability, neuroinflammation, and NCB in males.