Experimental gastritis leads to anxiety- and depression-like behaviors in female but not male rats
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RESEARCH
Open Access
Experimental gastritis leads to anxiety- and depression-like behaviors in female but not male rats Jia Luo1,2, Tao Wang1, Shan Liang1,2, Xu Hu1, Wei Li1,2 and Feng Jin1*
Abstract Human and animals studies support the idea that there is a gender-related co-morbidity of pain-related and inflammatory gastrointestinal (GI) diseases with psychological disorders. This co-morbidity is the evidence for the existence of GI-brain axis which consists of immune (cytokines), neural (vagus nerve) and neuroendocrine (HPA axis) pathways. Psychological stress causes disturbances in GI physiology, such as altered GI barrier function, changes in motility and secretion, development of visceral hypersensitivity, and dysfunction of inflammatory responses. Whether GI inflammation would exert impact on psychological behavior is not well established. We examined the effect of experimental gastritis on anxiety- and depression-like behaviors in male and female Sprague–Dawley rats, and evaluated potential mechanisms of action. Gastritis was induced by adding 0.1% (w/v) iodoacetamide (IAA) to the sterile drinking water for 7 days. Sucrose preference test assessed the depression-like behavior, open field test and elevated plus maze evaluated the anxiety-like behavior. IAA treatment induced gastric inflammation in rats of either gender. No behavioral abnormality or dysfunction of GI-brain axis was observed in male rats with IAA-induced gastritis. Anxiety- and depression-like behaviors were apparent and the HPA axis was hyperactive in female rats with IAA-induced gastritis. Our results show that gastric inflammation leads to anxiety- and depression-like behaviors in female but not male rats via the neuroendocrine (HPA axis) pathway, suggesting that the GI inflammation can impair normal brain function and induce changes in psychological behavior in a gender-related manner through the GI-to-brain signaling. Keywords: Gastrointestinal-brain axis, Iodoacetamide-induced gastritis, Anxiety, Depression, Gender difference
Introduction The high co-morbidity between gastrointestinal (GI) diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and functional dyspepsia (FD), and psychological symptoms such as depression and anxiety is the evidence for existence of GI-brain axis [1-8]. Many researches on this field have focused on the pathogenic role of psychological stress based on the primary observation that psychological stress induces modifications of motility, secretion, visceral sensitivity, and local inflammatory responses in the GI tract [9,10]. However, in recent years a growing body of studies provides compelling evidences to suggest that not only can the brain affect GI * Correspondence: [email protected] 1 Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China Full list of author information is available at the end of the article
activity, but that the GI activity can also induce changes in brain function [11-13]. There are three potential path
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