Bacterial infection causes stress-induced memory dysfunction in mice
- Mélanie G Gareau1,
- Eytan Wine1,2,
- David M Rodrigues1,
- Joon Ho Cho3,
- Mark T Whary4,
- Dana J Philpott3,
- Glenda MacQueen5,
- Philip M Sherman1
- 1Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Canada
- 2Department of Pediatrics, Division of Gastroenterology and Nutrition, University of Alberta, Alberta, Canada
- 3Department of Immunology, University of Toronto, Toronto, Ontario, Canada
- 4Division of Comparative Medicine, Massachusetts Institute of Technology, Massachusetts, USA
- 5Department of Psychiatry, University of Calgary, Alberta, Canada
- Correspondence to Philip M Sherman, Cell Biology Program, Research Institute, Hospital for Sick Children, 555 University Ave, Rm 8409, Toronto, ON M5G 1X8, Canada;
- Revised 1 September 2010
- Accepted 3 September 2010
- Published Online First 21 October 2010
Background The brain–gut 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.
- bacterial pathogen
- behaviour stress
- brain/gut interaction
- colonic microflora
- infectious disease
- irritable bowel syndrome stress
Linked articles 226779.
See Commentary, p 288
Funding Crohn's and Colitis Foundation of Canada 600-60 St. Clair Avenue East Toronto, ON M4T 1N5. This work was provided by a Faye Shapiro Cutler Grant-In-Aid from the Crohn's and Colitis Foundation of Canada (PMS). CCFC/CAG/CIHR fellowship (MGG); Canada Research Chair in Gastrointestinal Disease (PMS).
Competing interests Portions of this work were funded by a research contract with Institut-Rosell Lallemand Inc, Montreal, Quebec, Canada.
Patient consent Not needed.
Provenance and peer review Not commissioned; externally peer reviewed.