Glucocorticoid-Mediated Regulation of BDNF and Autophagy in Dentate Gyrus Neurons

Chronic stress is an important risk factor for depression and is associated with sutained glucocorticoid signaling and impaired hippocampal function. Prolonged exposure to corticosterone, a major glucocorticoid, can distrpt adult hippocampal neurogenesis (AHN) in the dentate gyrus (DG) and reduce brain-derived neurotrophic factor (BDNF), which contributes to the differentiation and maturation of adult-born neurons through TrkB signaling. This review focuses on the studies showing that chronic CORT exposure increases neuronal autophagy in the DG and reduces BDNF levels, and disccus the current evidence linking CORT-induced neural autophagy to BDNF loss. While inhibition of autophagy can restore BDNF and partially rescue impaired AHN, whether GR mediates CORT-induced autophagy in DG neurons remain unanswered. In addition, GR signaling may influence BDNF through autophagy-independent mechanisms, including direct regulation of BDNF transcription. Together, the current studies supports a potential model in which GR-mediated autophay coontributes to intracellular BDNF loss following chornic CORT. This propsoed mechanism provides a direction for further examing how prolonged glucocorticoid signaling participates in impaired AHN.