Isolation stress for 30 days alters hepatic gene expression profiles, especially with reference to lipid metabolism in mice

Nakai, Yuji; Miyashita, Tomoya; Fukui, Yuichiro; Morita, Maki; Sanmiya, Kazutsuka; Sakakibara, Hiroyuki; Matsumoto, Ichiro; Abe, Keiko; Yakabe, Takafumi; Yajima, Nobuhiro; Shimoi, Kayoko

doi:10.1152/physiolgenomics.90358.2008

Cited by 22 publications

(21 citation statements)

References 53 publications

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“…Therefore, we were unable to keep male littermates of some of the wild-derived strains in the same cage. It has been reported that housing the mice for long periods in isolation tends to induce excessive stress that may interfere with our observations (Motoyama et al, 2009). Furthermore, we surmised that the social interaction would tend to synchronize all the individuals in a group, potentially making our subsequent form estimates of daily activity across subjects within a co-housed group more coherent (e.g.…”

Section: Materials and Methods Micementioning

confidence: 64%

Ultradian components in the locomotor activity rhythms of the genetically normal mouse,Mus musculus

Dowse

Umemori

Koide

2010

Journal of Experimental Biology

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SUMMARYUltradian periodicities in physiological processes have been reported for a wide variety of organisms and may appear as bouts in locomotor activity. In some instances, this temporal organization can be related to some ethological strategy. In mice, however, ultradian rhythms have been reported largely in animals with circadian pacemakers disrupted either by genetic or surgical manipulation. Using analysis techniques capable of resolving periodicities in the ultradian range in the presence of strong diel periodicity, we found unequivocal evidence of ultradian rhythms in mice entrained to an light:dark cycle. We collected locomotor activity data of individuals from 11 genetically disparate strains of mice whose activity was recorded in 12h:12h L:D photoperiods for 3days. Data were subjected to maximum entropy spectral analysis and autocorrelation, both before and after filtering to remove the 24-h periodicity. We found that every strain had a majority of individuals with strong ultradian rhythms ranging from 3 to ~5h. These periodicities were commonly visible in individual animals both in high-pass-filtered and in unfiltered data. Furthermore, when all raw data from a given strain were pooled to get a 24-h ensemble average across all animals and days, the rhythms continued to be discernable. We fitted Fourier series to these form estimates to model the frequency structure of each strain and found significant effects of strain and an interaction between period and strain indicating significant genetic variation for rhythmicity in the ultradian range. The techniques employed in this study should have wider use in a range of organisms and fields.

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Section: Materials and Methods Micementioning

confidence: 64%

Ultradian components in the locomotor activity rhythms of the genetically normal mouse,Mus musculus

Dowse

Umemori

Koide

2010

Journal of Experimental Biology

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“…We also have analyzed the hepatic gene expression profiles of the mice exposed to social isolation stress for 4 weeks using DNA microarrays. The lipid metabolism-related pathway through the peroxisome proliferator-activated receptor alpha subtype was remarkably down-regulated, and the lipid biosynthesis pathway controlled by sterol regulatory element binding factor 1 was significantly up-regulated without changing body weight compared with the control (Motoyama et al, 2009). Above all, these results led us to hypothesize that prolonged social isolation stress for more than 4 weeks would activate lipid biosynthesis and enhance energy accumulation, particularly in the liver, and result in excess weight gain and hepatic hypertrophy.…”

Section: Introductionmentioning

confidence: 93%

“…We recently investigated the biological responses of mice exposed to social stress comprising isolation with a reduced volume of bedding (2 g/cage) (Miyashita et al, 2006;Nishio et al, 2007;Motoyama et al, 2009). In our system, the control group was the grouped-housing (5 mice/cage) with a standard volume of bedding (40 g/cage).…”

Section: Introductionmentioning

confidence: 99%

Social isolation stress induces hepatic hypertrophy in C57BL/6J mice

et al. 2012

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-We previously reported that social isolation stimulated a stress response leading to increasing plasma corticosterone level and disruption of the hepatic lipid metabolism-related pathway, without changing body and organ weights, in mice after 4 weeks of social isolation stress, compared with the grouped-housing control (5 mice/cage). In this study, we evaluated the effects of social isolation stress for an extended period on physiologic changes in male C57BL/6J mice. Plasma corticosterone was reduced after 13 weeks, indicating mice might adapt to social isolation stress. However, body and visceral fat weights were significantly increased in combination with hepatic hypertrophy, and significant decreases in levels of triglyceride and adiponectin in plasma were observed. In conclusion, it is tempting to speculate that mice exposed to social isolation stress for 13 continuous weeks could be at an increased risk of overweight with hepatic hypertrophy. Our results also imply that physiological changes, at least fatty acid metabolism, under stress exposure might be an important factor when evaluating the chronic effects of environmental chemicals.

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“…1 Stress modulates gene expression, behavior, metabolism and immune function. 2, 3, 4, 5 Chronic stress has been shown to impair lymphocyte proliferation, vaccination efficacy, 6, 7, 8, 9 wound healing 10, 11 and natural killer (NK) cell activity, and to increase the risk for bacterial and viral infection 12 and cancer. 13 Comprehensive descriptions of stress-affected molecular networks and pathways are needed to reveal strategies to reduce and prevent the pathophysiologic effects of prolonged intense stress.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome characterization of immune suppression from battlefield-like stress

et al. 2012

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Transcriptome alterations of leukocytes from soldiers who underwent 8 weeks of Army Ranger training (RASP, Ranger Assessment and Selection Program) were analyzed to evaluate impacts of battlefield-like stress on the immune response. About 1400 transcripts were differentially expressed between pre- and post-RASP leukocytes. Upon functional analysis, immune response was the most enriched biological process, and most of the transcripts associated with the immune response were downregulated. Microbial pattern recognition, chemotaxis, antigen presentation and T-cell activation were among the most downregulated immune processes. Transcription factors predicted to be stress-inhibited (IRF7, RELA, NFκB1, CREB1, IRF1 and HMGB) regulated genes involved in inflammation, maturation of dendritic cells and glucocorticoid receptor signaling. Many altered transcripts were predicted to be targets of stress-regulated microRNAs. Post-RASP leukocytes exposed ex vivo to Staphylococcal enterotoxin B showed a markedly impaired immune response to this superantigen compared with pre-RASP leukocytes, consistent with the suppression of the immune response revealed by transcriptome analyses. Our results suggest that suppression of antigen presentation and lymphocyte activation pathways, in the setting of normal blood cell counts, most likely contribute to the poor vaccine response, impaired wound healing and infection susceptibility associated with chronic intense stress.

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Isolation stress for 30 days alters hepatic gene expression profiles, especially with reference to lipid metabolism in mice

Abstract: . Isolation stress for 30 days alters hepatic gene expression profiles, especially with reference to lipid metabolism in mice.

Cited by 22 publications

References 53 publications

Ultradian components in the locomotor activity rhythms of the genetically normal mouse,Mus musculus

Ultradian components in the locomotor activity rhythms of the genetically normal mouse,Mus musculus

Social isolation stress induces hepatic hypertrophy in C57BL/6J mice

Transcriptome characterization of immune suppression from battlefield-like stress

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