Bacterial infection causes stress-induced memory dysfunction in mice

被引:691
作者
Gareau, Melanie G.
Wine, Eytan [2 ]
Rodrigues, David M.
Cho, Joon Ho [3 ]
Whary, Mark T. [4 ]
Philpott, Dana J. [3 ]
MacQueen, Glenda [5 ]
Sherman, Philip M. [1 ]
机构
[1] Univ Toronto, Hosp Sick Children, Res Inst, Cell Biol Program, Toronto, ON M5G 1X8, Canada
[2] Univ Alberta, Div Gastroenterol & Nutr, Dept Pediat, Edmonton, AB T6G 2M7, Canada
[3] Univ Toronto, Dept Immunol, Toronto, ON, Canada
[4] MIT, Div Comparat Med, Cambridge, MA 02139 USA
[5] Univ Calgary, Dept Psychiat, Calgary, AB T2N 1N4, Canada
关键词
IRRITABLE-BOWEL-SYNDROME; CITROBACTER-RODENTIUM INFECTION; MURINE COLONIC HYPERPLASIA; CHRONIC PSYCHOLOGICAL STRESS; INTESTINAL BARRIER FUNCTION; MATERNAL SEPARATION; ESCHERICHIA-COLI; SYNAPTIC PLASTICITY; SPATIAL MEMORY; C-FOS;
D O I
10.1136/gut.2009.202515
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background The brainegut axis is a key regulator of normal intestinal physiology; for example, psychological stress is linked to altered gut barrier function, development of food allergies and changes in behaviour. Whether intestinal events, such as enteric bacterial infections and bacterial colonisation, exert a reciprocal effect on stress-associated behaviour is not well established. Objective To determine the effects of either acute enteric infection or absence of gut microbiota on behaviour, including anxiety and non-spatial memory formation. Methods Behaviour was assessed following infection with the non-invasive enteric pathogen, Citrobacter rodentium in both C57BL/6 mice and germ-free Swiss-Webster mice, in the presence or absence of acute water avoidance stress. Whether daily treatment with probiotics normalised behaviour was assessed, and potential mechanisms of action evaluated. Results No behavioural abnormalities were observed, either at the height of infection (10 days) or following bacterial clearance (30 days), in C rodentium-infected C57BL/6 mice. When infected mice were exposed to acute stress, however, memory dysfunction was apparent after infection (10 days and 30 days). Memory dysfunction was prevented by daily treatment of infected mice with probiotics. Memory was impaired in germ-free mice, with or without exposure to stress, in contrast to conventionally reared, control Swiss-Webster mice with an intact intestinal microbiota. Conclusions The intestinal microbiota influences the ability to form memory. Memory dysfunction occurs in infected mice exposed to acute stress, while in the germ-free setting memory is altered at baseline.
引用
收藏
页码:307 / 317
页数:11
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