From Gut to Brain: Alteration in Inflammation Markers in the Brain of Dextran Sodium Sulfate-induced Colitis Model Mice

Abstract

Objective: Neuropsychiatric manifestations like depression and cognitive dysfunction commonly occur in inflammatory bowel disease (IBD). In the context of the brain-gut axis model, colitis can lead to alteration of brain function in a bottom-up manner. Here, the changes in the response of the hypothalamic-pituitary-adrenal axis and inflammationrelated markers in the brain in colitis were studied. Methods: Dextran sodium sulfate (DSS) was used to generate a mouse model of colitis. Mice were treated with DSS for 3 or 7 days and sacrificed. We analyzed the gene expression of brain-derived neurotrophic factor (BDNF), cyclooxygenase 2 (COX-2), and glial fibrillary acidic protein (GFAP), and the expression of GFAP, in the hippocampus, hypothalamus, and amygdala. Additionally, the levels of C-reactive protein (CRP) and serum cortisol/corticosterone were measured. Results: Alteration of inflammatory-related markers varied depending on the brain region and exposure time. In the hippocampus, COX-2 mRNA, GFAP mRNA, and GFAP expression were upregulated during exposure to DSS. However, in the hypothalamus, COX-2 mRNA was upregulated only 3 days after treatment. In the amygdala, BDNF and COX-2 mRNAs were downregulated. CRP and corticosterone expression increased with DSS treatment at day 7. Conclusion: IBD could lead to neuroinflammation in a bottom-up manner, and this effect varied according to brain region. Stress-related hormones and serum inflammatory markers, such as CRP, were upregulated from the third day of DSS treatment. Therefore, early and active intervention is required to prevent psychological and behavioral changes caused by IBD, and region-specific studies can help understand the precise mechanisms by which IBD affects the brain.

Electroacupuncture and Moxibustion Regulate Hippocampus Glia and Mitochondria Activation in DSS‐Induced Colitis Mice

“…Although IBD is a kind of gastrointestinal disease, characterized by chronic intestinal inflammation, dysregulated immune responses to intestinal microbiota, and dysfunction of the epithelial barrier [6], several studies have shown the presence of neuropsychiatric manifestations, such as depression and cognitive dysfunction, particularly during the active stage of the disease [7][8][9][10]. In a previous study, we also observed that DSS-induced colitis was accompanied with anxiety behavior [11].…”

“…Similarly, in pathological conditions, such as IBD and PD, the dysregulation of norepinephrine, epinephrine, dopamine, and serotonin neurotransmitters levels can lead to a variety of gastrointestinal symptoms [15]. Also, rats with colitis showed increased hippocampal excitability and cortical inflammation [7,14,16]. In acute DSS-induced colitis mice, the expression of IL-6, TNF-α elevated, and microglia was activated in the brain tissue.…”

Variant-to-Gene-Mapping Analyses Reveal a Role for the Hypothalamus in Genetic Susceptibility to Inflammatory Bowel Disease

“…16 However, the possible physiological links between depression and IBD remain unclear. 17 Stress as a comorbid factor in both IBD and depression render the hypothalamus a possible mediator of IBD.…”

Neuroimmune Responses Mediate Depression-Related Behaviors following Acute Colitis

“…Among these, the hippocampus is a key brain region within the limbic system that has been linked to depression in both humans and rodents (Dantzer et al., 2008), and during depressive states, there is a dysregulation of several neurotransmitter systems such as the serotonergic, noradrenergic, and GABAergic systems. mRNA levels of specific inflammatory markers, such as for COX-2, are upregulated in the hippocampus of mice with visceral inflammation (Do and Woo, 2018), and prolonged pharmacologically induced visceral inflammation gives rise to reduced hippocampal neurogenesis (Zonis et al., 2015). In addition, there is an inflammatory component to depression, as evident from alterations of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) levels in the limbic system of patients with depression (Hodes et al., 2015).…”