Hypothalamic orexin prevents hepatic insulin resistance induced by social defeat stress in mice

Tsuneki, Hiroshi; Tokai, Emi; Sugawara, Chieko; Wada, Tsutomu; Sakurai, Takeshi; Sasaoka, Toshiyasu

doi:10.1016/j.npep.2013.02.002

Cited by 30 publications

(15 citation statements)

References 41 publications

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“…This is consistent with numerous studies that found that CSDS induces an increase in body weight [52–56], which may result from stress-related hyperphagia or a metabolic aberration. However, the stress-induced increase in body weight was not affected by kososan extract treatment, suggesting that the observed behavioral recovery may be independent of mechanisms that influence body weight.…”

Section: Discussionsupporting

confidence: 93%

Kososan, a Kampo medicine, prevents a social avoidance behavior and attenuates neuroinflammation in socially defeated mice

Ito

Hirose

Ishida

et al. 2017

J Neuroinflammation

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BackgroundKososan, a Kampo (traditional Japanese herbal) medicine, has been used for the therapy of depressive mood in humans. However, evidence for the antidepressant efficacy of kososan and potential mechanisms are lacking. Recently, it has been recognized that stress triggers neuroinflammation and suppresses adult neurogenesis, leading to depression and anxiety. Here, we examined whether kososan extract affected social behavior in mice exposed to chronic social defeat stress (CSDS), an animal model of prolonged psychosocial stress, and neuroinflammation induced by CSDS.MethodsIn the CSDS paradigm, C57BL/6J mice were exposed to 10 min of social defeat stress from an aggressive CD-1 mouse for 10 consecutive days (days 1–10). Kososan extract (1.0 g/kg) was administered orally once daily for 12 days (days 1–12). On day 11, the social avoidance test was performed to examine depressive- and anxious-like behaviors. To characterize the impacts of kososan on neuroinflammation and adult neurogenesis, immunochemical analyses and ex vivo microglial stimulation assay with lipopolysaccharide (LPS) were performed on days 13–15.ResultsOral administration of kososan extract alleviated social avoidance, depression- and anxiety-like behaviors, caused by CSDS exposure. CSDS exposure resulted in neuroinflammation, as indicated by the increased accumulation of microglia, the resident immune cells of the brain, and their activation in the hippocampus, which was reversed to normal levels by treatment with kososan extract. Additionally, in ex vivo studies, CSDS exposure potentiated the microglial pro-inflammatory response to a subsequent LPS challenge, an effect that was also blunted by kososan extract treatment. Indeed, the modulatory effect of kososan extract on neuroinflammation appears to be due to a hippocampal increase in an anti-inflammatory phenotype of microglia while sparing an increased pro-inflammatory phenotype of microglia caused by CSDS. Moreover, reduced adult hippocampal neurogenesis in defeated mice was recovered by kososan extract treatment.ConclusionsOur findings suggest that kososan extract prevents a social avoidant behavior in socially defeated mice that is partially mediated by the downregulation of hippocampal neuroinflammation, presumably by the relative increased anti-inflammatory microglia and regulation of adult hippocampal neurogenesis. Our present study also provides novel evidence for the beneficial effects of kososan on depression/anxiety and the possible underlying mechanisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0876-8) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 93%

Kososan, a Kampo medicine, prevents a social avoidance behavior and attenuates neuroinflammation in socially defeated mice

Ito

Hirose

Ishida

et al. 2017

J Neuroinflammation

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“…6A). Social defeat stress42, which was produced by 10 min of direct interaction followed by 110 min of indirect interaction between a male intruder Bmal1-Eluc mouse and a resident ICR mouse at ZT4–6 over 3 consecutive days, caused clear phase-advance of bioluminescence rhythms in the kidneys, livers, and submandibular glands of the intruder mice (Fig. 6B).…”

Section: Resultsmentioning

confidence: 99%

“…Elevated platform stress was administered by placing individual mice on a small stage (10 × 10 cm) at a height of 50 cm from the floor. Bmal1-ELuc intruder mice were subjected to social defeat stress by transferring them to cages of ICR mice (one intruder per resident mouse)42. Mice were allowed free contact with each other for the first 10 min; a wire mesh was then placed between them for 110 min to prevent fighting while still permitting interaction, after which intruders were returned to their home cages.…”

Section: Methodsmentioning

confidence: 99%

Entrainment of the mouse circadian clock by sub-acute physical and psychological stress

Tahara

Shiraishi

Kikuchi

et al. 2015

Sci Rep

117

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The effects of acute stress on the peripheral circadian system are not well understood in vivo. Here, we show that sub-acute stress caused by restraint or social defeat potently altered clock gene expression in the peripheral tissues of mice. In these peripheral tissues, as well as the hippocampus and cortex, stressful stimuli induced time-of-day-dependent phase-advances or -delays in rhythmic clock gene expression patterns; however, such changes were not observed in the suprachiasmatic nucleus, i.e. the central circadian clock. Moreover, several days of stress exposure at the beginning of the light period abolished circadian oscillations and caused internal desynchronisation of peripheral clocks. Stress-induced changes in circadian rhythmicity showed habituation and disappeared with long-term exposure to repeated stress. These findings suggest that sub-acute physical/psychological stress potently entrains peripheral clocks and causes transient dysregulation of circadian clocks in vivo.

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“…Insulin resistance frequently develops during acute or chronic stress (Tsuneki et al, 2013). Insufficient insulin secretion to compensate for insulin resistance is also the characteristic of Type 2 diabetes.…”

Section: Stress Inflammation and Diseasesmentioning

confidence: 99%

Inflammation: The Common Pathway of Stress-Related Diseases

Liu

Wang

Jiang

2017

Front. Hum. Neurosci.

566

333

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While modernization has dramatically increased lifespan, it has also witnessed that the nature of stress has changed dramatically. Chronic stress result failures of homeostasis thus lead to various diseases such as atherosclerosis, non-alcoholic fatty liver disease (NAFLD) and depression. However, while 75%–90% of human diseases is related to the activation of stress system, the common pathways between stress exposure and pathophysiological processes underlying disease is still debatable. Chronic inflammation is an essential component of chronic diseases. Additionally, accumulating evidence suggested that excessive inflammation plays critical roles in the pathophysiology of the stress-related diseases, yet the basis for this connection is not fully understood. Here we discuss the role of inflammation in stress-induced diseases and suggest a common pathway for stress-related diseases that is based on chronic mild inflammation. This framework highlights the fundamental impact of inflammation mechanisms and provides a new perspective on the prevention and treatment of stress-related diseases.

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Hypothalamic orexin prevents hepatic insulin resistance induced by social defeat stress in mice

Cited by 30 publications

References 41 publications

Kososan, a Kampo medicine, prevents a social avoidance behavior and attenuates neuroinflammation in socially defeated mice

Kososan, a Kampo medicine, prevents a social avoidance behavior and attenuates neuroinflammation in socially defeated mice

Entrainment of the mouse circadian clock by sub-acute physical and psychological stress

Inflammation: The Common Pathway of Stress-Related Diseases

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