Fig. 2.

BDNF response after inflammatory brain pathogenicity. In chronically stressful situations, such as brain pathologies, there is an induction of NF-κB-dependent pro-inflammatory activation of microglia after induction of the pattern recognition receptor (PRR) by the challenge (e.g., stress or pathology). Pro-inflammatory cytokines, especially IL-1, can directly bind microglial cells, which result in induction of the expression and release of several mediators, most of which are neurotoxic, including reactive oxygen (ROS) and nitrogen species (RNS), pro-inflammatory cytokines (such as tumor necrosis factor), and chemokines (such as CC-chemokine ligand 2, CCL2; also known as MCP1). Additionally, there is a decrease of BDNF signaling in the synaptic cleft, further reducing BDNF-dependent survival-related signaling (black dashed lines) and inhibition of apoptotic pathways, such as glycogen synthase kinase 3-beta (GSK-3: red dashed line). Such factors will lead to an increase of NF-κB complex binding to genes that express pro-inflammatory cytokines (e.g., interleukin 1-β, IL-6, IL-8, TNF). The effect of transactivation factors on the BDNF-independent maintenance of TrkB is not clear yet