Possible role of the NLRP3 inflammasome and the gut-brain axis in multiple sclerosis-related depression.

ABSTRACT

Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system that results from complex interactions between genetic and environmental determinants. Patients with MS exhibit a high risk of depression, however, the exact pathomechanisms remain largely unknown. It is becoming widely accepted that the gut-brain axis (GBA) disorders may exert an influence on neuroinflammation and psychiatric symptoms, including so-called MS-related depression. The element suggested as a bridge between intestinal disorders, depression, and MS is an inflammatory response with the central role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The pro-inflammatory activity of effector cytokines of the NLRP3 inflammasome forms the hypothesis that it is actively involved in the development of inflammatory and autoimmune diseases. Despite extensive reviews considering the possible origins of MS-related depression, its complex pathophysiology prevents any easy determination of its underlying mechanisms. This paper aims to discuss molecular mechanisms related to the GBA axis that can mediate dysbiosis, intestinal barrier dysfunction, disruption of blood-brain barrier integrity, neuroinflammation, and subsequent manifestation of MS-related major depressive disorder.