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. 2009 Jun;10(6):597-603.
doi: 10.1016/j.sleep.2008.12.009. Epub 2009 Apr 28.

Sleep Deprivation Worsens Inflammation and Delays Recovery in a Mouse Model of Colitis

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Free PMC article

Sleep Deprivation Worsens Inflammation and Delays Recovery in a Mouse Model of Colitis

Yueming Tang et al. Sleep Med. .
Free PMC article

Abstract

Background and aim: We recently showed that patients with inflammatory bowel disease (IBD) report significantly more sleep disturbances. To determine whether disrupted sleep can affect the severity of inflammation and the course of IBD, we used an animal model of colonic inflammation to determine the effects of acute and chronic intermittent sleep deprivation on the severity of colonic inflammation and tissue damage in colitis and recovery from this damage.

Methods: Acute sleep deprivation (ASD) consisted of 24h of forced locomotor activity in a mechanical wheel rotating at a constant speed. Chronic intermittent sleep deprivation (CISD) consisted of an acute sleep deprivation episode, followed by additional sleep deprivation periods in the wheel for 6h every other day throughout the 10day study period. To induce colitis, mice were given 2% dextran sodium sulfate (DSS) in their daily drinking water for 7days. The development and severity of colitis were monitored by measuring weight loss and tissue myeloperoxidase (MPO) activity daily and colon histology scores 10days after initiation of colitis.

Results: ASD or CISD did not cause colonic inflammation in vehicle-treated mice. Changes in daily body weight, tissue MPO levels and colon histopathology score were similar between mice that were sleep deprived and controls. Daily DSS ingestion caused colitis in mice. ASD worsened colonic inflammation: tissue MPO levels in ASD/DSS-treated mice were significantly higher than in DSS-treated mice that were not sleep deprived. However, the worsening of colonic inflammation by ASD was not enough to exacerbate clinical manifestations of colitis such as weight loss. In contrast, the deleterious effects of CISD were severe enough to cause worsening of histological and clinical manifestations of colitis. The deleterious effects of sleep deprivation on severity of colitis appeared to be due to both increased colonic inflammation and a decrease in the ability of mice to recover from DSS-induced colonic injury.

Conclusion: Both acute and chronic intermittent sleep deprivation exacerbate colonic inflammation. Thus, sleep deprivation could be an environmental trigger that predisposes IBD patients to develop flare ups and a more severe disease course. These results provide a scientific rationale to conduct an interventional trial to determine whether improvement in sleep patterns will prevent IBD flare ups, modify the disease course, and improve quality of life.

Figures

Fig. 1
Fig. 1
Effect of acute and chronic intermittent sleep deprivation on weight loss in 2% DDS-induced colitis mice. Weight loss relative to the animal’s base weight before induction of colitis was measured daily as a biomarker for colitis. Acute sleep deprivation (ASD) was achieved by forced wheel walking for 24 h prior to the administration of 2% DSS (as indicated by the dotted box). Chronic intermittent sleep deprivation (CISD) was a combination of an acute 24 h period of sleep deprivation followed by 6 h of forced activity in the wheel every other day after day 1 (as indicated by the dashed boxes on the x-axis). ASD or CISD increased weight loss caused by 2% DSS. Animals in the ASD & CISD groups received 7 days of 2% DSS treatment in their drinking water. There was a significant difference in weight loss in the CISD groups compared with controls (2% DSS alone) during the recovery period (days 9 and 10). Data are expressed as mean ± SEM. *p < 0.05 compared with the no sleep deprivation control group.
Fig. 2
Fig. 2
Effect of sleep deprivation on severity of 2% DSS-induced colitis. (A) Disease symptom scores determined by stool consistency, overt blood and occult blood in stools are shown for days 5, 7 and 10 of DSS treatment. However, ASD and CISD did not show significant differences in DSS-induced colitis symptoms. (B) The colon length of each mouse was measured from the end of the cecum to the anus. Chronic intermittent sleep deprivation (CISD) significantly exacerbated the shortening of the colon induced by 2% DSS (#p < 0.05 compared with no DSS treatment group; *p < 0.05 compared with DSS treated alone group). (C) Histology scores as indicators of colonic inflammation and tissue injury induced by DSS. All animals were treated with 2% DSS. Scores were determined as detailed in Section 2. Compared with control animals (2% DSS treated), the score in the chronically sleep deprived mice (CISD group) was significantly higher, indicating a more severe colitis as a consequence of the sleep deprivation. Data are expressed as mean ± SEM. *p < 0.05 compared with non-deprived DSS-treated mice (no sleep deprivation, NSD + DSS, n = 8/group). (D) Representative sections of the distal colon on day 10 after the administration of the DSS. (a) Chronic intermittent sleep deprivation (CISD alone) did not significantly affect the histology of the colon. (b) Two percentage of DSS caused colitis with an inflammatory reaction and tissue injury with loss of crypts and mucosal ulceration. (c and d) Acute sleep deprivation (ASD) and chronic intermittent sleep deprivation (CISD) exacerbated the damage caused by 2% DSS.
Fig. 3
Fig. 3
Effect of sleep deprivation on colonic inflammation assessed by myeloperoxidase activity (MPO) in the colon. A high MPO value indicates increased colonic inflammation. Both acute sleep deprivation (ASD) and chronic intermittent sleep deprivation (CISD) significantly increased MPO activity in the colon. Data are expressed as mean ± SEM. (#p < 0.05 compared with no DSS treatment group; *p < 0.5 compared with DSS treated alone, but no sleep deprivation (NSD) group).

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