Implications of neurogenesis in depression through BDNF: rodent models, regulatory pathways, gut microbiota, and potential therapy

Major Depressive Disorder (MDD) is a prevalent psychiatric disorder with a profound impact on global health, necessitating a deeper understanding of its pathophysiology. This review synthesizes current evidence linking neurogenesis, particularly in the hippocampal region, with MDD. Accumulating data showed a significant reduction of neurogenesis in the hippocampal region of both MDD patients and various MDD rodent models. We highlight the role of brain-derived neurotrophic factor (BDNF) and its associated signaling pathways in regulating neurogenesis and depressive symptoms. Additionally, the influence of gut microbiota on the neurogenesis in depression is presented, offering a novel perspective on environmental modulation of neurogenesis. This review also underscores the potential antidepressant interventions targeting neurogenesis and BDNF’s regulation, such as therapeutic benefits of environmental enrichment, physical activity, and pharmacological agents in enhancing neurogenesis and alleviating depressive symptoms. Together, this systemic review provides a foundation for future research aiming at developing personalized treatments by targeting neurogenesis in MDD, potentially leading to novel biomarkers and therapeutic strategies.