Selected Publications
Gut inflammation drives changes in brain and behaviour in mouse models of inflammatory bowel disease
Gastrointestinal tract (gut) inflammation increases sickness behaviours. This includes stress and threat-coping behaviors, which are associated with altered activity in fear-related neural circuits, such as the basolateral amygdala and hippocampus. It remains to be determined whether inflammation from the gut affects neural activity by altering dendritic spines.
Chronic gut inflammation impairs contextual control of fear
Chronic inflammatory diseases are highly comorbid with anxiety in humans. The extent to which chronic inflammation is responsible for this relationship remains to be determined. Access the article here.
Most gastrointestinal diseases and disorders (GIDD) are associated with depression, anxiety, and cognitive dysfunction. This suggests that shared features of GIDD, particularly chronic pain and inflammation, affect specific neural targets. The critical review of clinical and animal research presented here reveals that anterior cingulate cortex (ACC) is a primary target. It is particularly sensitive to neuroinflammation, and its function accounts for altered mental function emergent in GIDD. Access the article here.
Chronic unpredictable stress shifts rat behavior from exploration to exploitation
Chronic stress evokes wide-ranging behavioral alterations, including risk avoidance, increased motoric output, and reduced consummatory behaviors. These are often interpreted as dysfunctions, but they may subserve adaptations for coping with existential threats.
Behavioral adaptations in a relapsing mouse model of colitis
Inflammatory bowel disease (IBD) is characterized by relapsing periods of gut inflammation, and is comorbid with depression, anxiety, and cognitive deficits. Animal models of IBD that explore the behavioral consequences almost exclusively use acute models of gut inflammation, which fails to recapitulate the cyclic, chronic nature of IBD. This study sought to identify behavioral differences in digging, memory, and stress-coping strategies in mice exposed to one (acute) or three (chronic) cycles of gut inflammation, using the dextran sodium sulfate (DSS) model of colitis.
Parasite-induced modulation of host immune responses as potential therapy for inflammatory gut disease
A recently identified feature of the host response to infection with helminth parasites is suppression of concomitant disease. Dendritic cells (DCs) exposed to antigens from the tapeworm Hymenolepis diminuta significantly reduce the severity of dinitrobenzene sulfonic acid–induced colitis in mice. Here we elucidate mechanisms underlying this cellular immunotherapy.
Infection with helminth parasites has been explored as a treatment for autoimmune and inflammatory diseases. As helminth antigens have potent immunomodulation properties capable of inducing regulatory programs in a variety of cell types, transferring cells treated with helminth antigens represents a novel extension to helminth therapy. Previous work determined that transfer of bone marrow-derived dendritic cells (DC) pulsed with a crude extract of the tapeworm Hymenolepis diminuta (HD) can suppress colitis in recipient mice. The present study explored the mechanism of disease suppression and the importance of interleukin (IL)-4 signaling.
Infection with helminth parasites and treatment with worm extracts can suppress inflammatory disease, including colitis. Postulating that dendritic cells (DCs) participated in the suppression of inflammation and seeking to move beyond the use of helminths per se, we tested the ability of Hymenolepis diminuta antigen‐pulsed DCs to suppress colitis as a novel cell‐based immunotherapy.