Neuroinflammatory Remodeling of the Anterior Cingulate Cortex as a Key Driver of Mood Disorders in Gastrointestinal Disease and Disorders

Abstract

The brain reciprocally communicates with the rest of the body via neural, endocrine, immune, and other systems. This is crucial for coordinating the complex behavioral and physiological responses needed to cope with the many challenges of life. The Anterior Cingulate Cortex (ACC) is a key brain structure involved in assessing rewards and threats, as well as activating appropriate responses. This is a dynamic process that depends on evolving needs and challenges. Important challenges include illness or injury. These typically involve inflammation and pain, which evoke neuroinflammatory processes in the brain to drive sickness behaviours. In the short term, sickness behaviours are considered adaptive, as they promote convalescence (e.g. low mood; lethargy, fatigue, social withdrawal), and enhanced threat appraisal (e.g. anxiety) to combat increased risk/vulnerability associated with sickness. Chronic inflammation, however, appears to remodel the system to inappropriately activate threat-coping responses, resulting in depressive and/or anxious phenotypes. These mood disorders are particularly pronounced in diseases and disorders associated with gut dysfunction, which feature chronic inflammation and altered ACC function. We propose that chronic inflammation remodels ACC physiology such that it errantly predicts heightened danger based on a mental model (a.k.a ‘schema’) of the world. This evokes chronic activation of threat-coping systems, including endocrine signaling (e.g. adrenaline), and anxiety. Inflammation can be driven by brain systems involving ACC, leading to a feedback-cycle that self-reinforces pathological states. This theory accounts for a wealth of clinical and preclinical data that implicate the ACC in disorders of mood and gastrointestinal function, and reveals a key player in the gut-brain axis that may represent a novel therapeutic target.

Targeting neuroinflammation with Abscisic Acid reduces pain sensitivity in females and hyperactivity in males of an ADHD mice model

“…Our result would agree with the notion that the ACC and pIC are primary targets for neuroinflammation. ACC has been associated with mood disorders and pain sensitivity [83]. Moreover, drug inhibition of pIC glia alleviates chronic pain in a rat model of nerve injury [84].…”

“…Our result would agree with the notion that the ACC and pIC are primary targets for neuroinflammation. ACC has been associated with mood disorders and pain sensitivity [83].…”

Sexual dysfunction worsen both the general and specific quality of life of women with irritable bowel syndrome. A cross-sectional study

“…[31] We believe this is an interesting route to study for later research. [32] IBS-QOL has lower scores in IBS patients and it is almost similar in SxD women (except for body image). This nding is congruent with those previously reported.…”

Inflammatory Animal Models of Parkinson’s Disease

“…All this information has encouraged some authors to deepen their understanding of the effects of peripheral inflammation on neuroinflammation. These studies have revealed that peripheral inflammation, especially gut inflammation, induces neuroinflammation in certain brain structures that is accompanied by several manifestations such as anxiety, depression, chronic pain and memory and cognitive impairments [149,150]. However, this neuroinflammation and its associated symptoms decrease with some antiinflammatory interventions in animal models.…”