Chronic stress-induced alterations in mouse colonic 5-HT and defecation responses are strain dependent

Chronic stress-induced alterations in mouse colonic 5-HT and defecation responses are strain dependent
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DOI:
10.3109/10253890.2011.607524
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发表时间:
2012-03-01
影响因子:
2.3
通讯作者:
Cryan, John F.
Cryan, John F.
中科院分区:
心理学4区
文献类型:
--
作者:
Julio-Pieper, Marcela;O'Mahony, Cliona M.;Cryan, John F.

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情绪障碍和慢性压力经常与胃肠道(GI)症状有关,包括腹泻或便秘。局部产生的5-羟色胺[5-羟色胺(5-HT)]调节胃肠动力,是应激相关胃肠道疾病病理生理学中的关键因素。我们的目的是确定慢性应激是否会对两个近交系小鼠的粪便排泄量和结肠5-羟色胺浓度产生不同的影响:Balb/c和C57BL/6,这两个品系的近交系小鼠应对应激的能力不同。成年雄性BALB/c和C57BL/6小鼠每天束缚2小时,连续10天。在每次应激过程中都会监测排便情况。在最后一次应激24小时后,两个品系的血浆皮质酮浓度都高于对照组,表明慢性应激的生理效应;然而,应激诱导的腹泻在C57BL/6小鼠中更为持久。C57BL/6小鼠结肠5-羟色胺的基础浓度较高,而应激只引起该品系小鼠结肠5-羟色胺的增加。幼龄BALB/c小鼠对5-羟色胺(0.33 mg/kg,ip)有较高的敏感性(腹泻发生率)。而不是C57BL/6小鼠。我们的结果表明,对应激的不同排便反应可能与结肠5-羟色胺浓度有关,这可能反过来反映了个体对5-羟色胺的敏感性。此外,C57BL/6小鼠作为研究慢性应激引起的胃肠道改变的相关模型出现。
Mood disorders and chronic stress are frequently associated with gastrointestinal (GI) symptoms including diarrhoea or constipation. Locally produced serotonin [5-hydroxytryptamine (5-HT)] regulates GI motility and is a key factor in the pathophysiology of stress-associated GI disorders. We aimed to establish whether chronic stress can differentially affect faecal output and colon 5-HT concentration in two inbred mouse strains: BALB/c and C57BL/6 which differ in their ability to cope with stress. Adult male BALB/c and C57BL/6 mice were restrained for 2 h daily for 10 days. Defecation was monitored during each stress session. Twenty-four hours after the last session of stress, plasma corticosterone concentration was higher than control in both strains, indicative of a physiological effect of chronic stress; however, stress-induced diarrhoea was more persistent in C57BL/6 mice. Basal concentration of colon 5-HT was higher in C57BL/6 mice, and stress elicited an increase in colon 5-HT only in this strain. Finally, naive BALB/c mice had a higher sensitivity (incidence of diarrhoea) to 5-HT (0.33 mg/kg, i.p.) than C57BL/6 mice. Our results suggest that differential defecation responses to stress may be associated with colon 5-HT concentration, which may in turn reflect the individual sensitivity to 5-HT. In addition, C57BL/6 mice emerge as a relevant model for studying GI alterations induced by chronic stress.