The role of enteric nervous system and GDNF in depression: conversation between the brain and the gut

Depression is a debilitating mental disorder that causes a persistent feeling of sadness and loss of interest. Approximately 280 million individuals worldwide suffer from depression by 2023. Despite the heavy medical and social burden imposed by depression, pathophysiology remains incompletely understood. Emerging evidence indicates various bidirectional interplay enable communication between the gut and brain. This interplay provides a link between intestinal and central nervous system as well as feedback from cortical and sensory centers to enteric activities, which also influences physiology and behavior in depression. This review aims to overview the significant role of the enteric nervous system (ENS) in the pathophysiology of depression and gut-brain axis's contribution to depressive disorders. Additionally, we explore the alterations in enteric glia cells (EGCs) and glial cell line-derived neurotrophic factor (GDNF) in depression and their involvement in neuronal support, intestinal homeostasis maintains and immune response activation. Modulating ENS function, EGCs and GDNF level could serve as novel strategies for future antidepressant therapy.