Figure 6. Model of BDNF role in MDD- and stress-related molecular and behavioral phenotypes.

Results from the current study suggest a sequence of events associated with MDD-related brain changes. First, prolonged stress induces selective deficit of dendritic BDNF indicated by low BDNF L- 3’-UTR expression in the PFC. Second, reduced BDNF supply to dendritic compartments and GABA interneurons targeting distal dendrites of pyramidal cells leads to impaired function of dendritic-targeting interneurons (e.g. downregulation of SST and GABA synthesizing enzyme), disrupted dendritic integrity, altered filtering and processing of excitatory input onto pyramidal cell dendrites, and finally, mood dysregulation.