Toward a better understanding of the central consequences of intestinal inflammation

Abstract

Inflammatory bowel diseases (IBDs), which include Crohn's disease and ulcerative colitis, are inflammatory diseases of the gastrointestinal tract. Quality of life for IBD patients is negatively affected by associated pain and gastrointestinal dysfunction, but also by serious behavioral symptoms that include depression, anxiety, fatigue, and cognitive dysfunction. Because these behavioral comorbidities are poorly understood, we have investigated them in a rat model of IBD caused by infusion of a hapten (trinitrobenzene sulfonic acid (TNBS)) into the lower colon. TNBS colitis has many similarities to Crohn's disease, and we have found that it is associated with changes in central nervous system function. TNBS-treated animals have lowered seizure thresholds, which resolve following remission, and hippocampal slices from such animals display increased excitability. There are significant changes in excitatory, AMPA receptor-mediated transmission, in part due to increased numbers of AMPA receptors lacking the GluR2 subunit. Long-term potentiation and depression are reduced in colitic animals, and the synaptic alterations are reversed if microglial activation and tumor necrosis factor α synthesis within the brain are blocked.

Cytokine‐mediated blood brain barrier disruption as a conduit for cancer/chemotherapy‐associated neurotoxicity and cognitive dysfunction

“…A number of intestinal pathologies are associated with an increased risk of behavioral comorbidities as indicated by increased rates of depression, mood disorders and cognitive dysfunction in patients with inflammatory bowel disease (IBD). 87 For example, elevated circulating proinflammatory cytokines, increased in intestinal permeability and the number of circulating monocytes are commonly reported in acute phases of trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. 88 Importantly, these are accompanied by localized breaches in the BBB 89 leading to increased neuroinflammation 90,91 and associated cognitive disturbance.…”

Activation of Dopamine D2 Receptor Alleviates Neuroinflammation and Neuronal Injury in Mice Model of Allergic Rhinitis With Olfactory Dysfunction

“…Recently, the anti-neuroin ammatory effects of the dopamine D2 receptor have been highlighted, and its agonists prevent the degeneration of dopaminergic neurons by inhibiting the TLR4/NF-κB pathway in PD mice [11]. Furthermore, the microglia-dependent TLR4/NF-κB pathway is a key link in inducing neuronal AMPA receptor (AMPAR) tra cking and subsequent excitotoxicity injury [11], which plays an important role in brain damage in many in ammatory diseases, such as peripheral in ammatory pain, autoimmune encephalopathy, brain injury, in ammatory bowel disease and others [12][13][14][15]. For example, the activation of glial purinergic signals by TLR4 can signi cantly increase the excitatory synaptic drive of CA1 neurons by modulating glutamate receptor tra cking [16].…”

The Perception of Physician Empathy by Patients with Inflammatory Bowel Disease

“…Nowadays, the pathogenesis is better understood, and a current concept of the disease is a breakdown of the intestinal epithelial barrier with infiltration by cells of the innate and adaptive immune systems, which release a number of cytokines. These cytokines may pass the blood-brain barrier and cause neurologic and behavioral changes [1]. The early onset and need for lifelong treatment are responsible for a high burden of disease and reduced quality of life [2].…”