It is becoming increasingly evident that peripheral organ centered inflammatory diseases, including chronic inflammatory liver diseases, are associated with changes in central neural transmission that result in alterations in behavior.
These behavioral changes include sickness behaviors such as fatigue, cognitive dysfunction, mood disorders, and sleep disturbances. [‘Sickness behaviors’ are manifestations of the body’s diversion of energy priorities to cope with infection.]
While such behaviors have a significant impact on patient quality of life, the changes within the brain and the communication pathways between the liver and the brain that give rise to changes in central neural activity are not fully understood.
Traditionally, neural and humoral [nervous system and immune system] communication pathways have been described, with the three cytokines TNF-alpha, IL-1beta and IL-6 receiving the most attention in mediating communication between the periphery and the brain, in the setting of peripheral inflammation.
However, more recently we have described an immune mediated communication pathway in experimentally induced liver inflammation whereby:
• In response to activation of resident immune cells in the brain (i.e. the microglia),
• Peripheral circulating monocytes transmigrate into the brain [monocytes are white blood cells that attack bacteria or viruses]
• Leading to sickness behavior development.
These signaling pathways drive changes in behavior by altering central neurotransmitter systems.
Specifically, changes in serotonergic and corticotropin releasing hormone neurotransmission have been demonstrated and implicated in liver inflammation- associated sickness behaviors.
Understanding how the liver communicates with the brain in the setting of chronic inflammatory liver diseases will help to delineate novel therapeutic targets that can reduce the burden of symptoms in patients with liver disease.
[Note: Interestingly, recent Scripps Institute Alzheimer’s research suggests that Alzheimer’s may originate in the liver: That is, based on animal studies, beta-amyloid appears to originate outside the brain, in the liver, enter the circulation and infiltrate the brain. With implications for new avenues of Alzheimer’s intervention research.]
Source: American Journal of Physiology, Gastrointestinal and Liver Physiology, Aug 25, 2011. PMID:21868631, by D’Mello C, Swain MG. Synder Institute of Infection, Immunity & Inflammation, Liver Unit, University of Calgary, Alberta, Canada. [Email: email@example.com]