Dextran sulfate sodium-induced colitis alters stress-associated behaviour and neuropeptide gene expression in the amygdala-hippocampus network of mice

Abstract

Psychological stress causes disease exacerbation and relapses in inflammatory bowel disease (IBD) patients. Since studies on stress processing during visceral inflammation are lacking, we investigated the effects of experimental colitis as well as psychological stress on neurochemical and neuroendocrine changes as well as behaviour in mice. Dextran sulfate sodium (DSS)-induced colitis and water avoidance stress (WAS) were used as mouse models of colitis and mild psychological stress, respectively. We measured WAS-associated behaviour, gene expression and proinflammatory cytokine levels within the amygdala, hippocampus and hypothalamus as well as plasma levels of cytokines and corticosterone in male C57BL/6N mice. Animals with DSS-induced colitis presented with prolonged immobility during the WAS session, which was associated with brain region-dependent alterations of neuropeptide Y (NPY), NPY receptor Y1, corticotropin-releasing hormone (CRH), CRH receptor 1, brain-derived neurotrophic factor and glucocorticoid receptor gene expression. Furthermore, the combination of DSS and WAS increased interleukin-6 and growth regulated oncogene-α levels in the brain. Altered gut-brain signalling in the course of DSS-induced colitis is thought to cause the observed distinct gene expression changes in the limbic system and the aberrant molecular and behavioural stress responses. These findings provide new insights into the effects of stress during IBD.

High-fat diet induces depression-like behaviour in mice associated with changes in microbiome, neuropeptide Y, and brain metabolome

“…These slices were placed on a cold plate (Weinkauf Medizintechnik, Forchheim, Germany) set at −18°C, on which prefrontal cortex (Bregma, +3.20 to −0.22), striatum (Bregma, +1.70 to −1.94), hypothalamus (Bregma, +0.26 to −2.92), and hippocampus (Bregma, −0.94 to −4.04) were microdissected with an iris spatula. 17 The microdissected brain areas were kept in homogenisation tubes on dry ice and subsequently stored at −70°C until further processing.…”

Fucose Ameliorates Tryptophan Metabolism and Behavioral Abnormalities in a Mouse Model of Chronic Colitis

“…One of the well-known IBD aspects well recapitulated in DSS-induced colitis model is the alteration of the host behavior. Anxiety-like behavior, decreased locomotion, reduced social interaction, alterations in expression of neuropeptide Y, and Brain Derived Neurotrophic Factor (BDNF) were reported upon DSS treatment in mice [5,6,19,20]. However, possible pathways underlying the gut-brain interactions are still discussed.…”

Dextran Sodium Sulphate (DSS)-Induced Colitis Alters the Expression of Neurotrophins in Smooth Muscle Cells of Rat Colon

“…Neurotrophins expression is altered differentially during colitis and has been linked to changes in gut motility (Geboes and Collins 1998, Reinshagen et al 2002, Johansson et al 2007 Additionally, up regulation of neurotrophins in spinal cord and dorsal root ganglion in response to inflammation plays a role in visceral hypersensitivity and the pathogenesis of inflammatory bowel disease and irritable bowel syndrome (Sharon et al 2012). Dextran sulfate sodium (DSS)-induced colitis is a well-established model to study inflammatory bowel diseases (IBD) such as colitis (Alkahtani et al 2013, Liu et al 2014, Reichmann et al 2015. Changes in neurotrophins' levels have been reported in IBD patients and in colitis models as well.…”