Figure 2.

Key elements of the limbic HPA. Glucocorticoids feed back to the brain to restrain the stress response. They produce their actions via GRs and MRs, which are generally classified as ligand-dependent transcription factors that are expressed in multiple brain regions, especially the hippocampus. Glucocorticoid effects in the brain involve not only direct and indirect genomic actions, but also direct stimulation of glutamate release and stimulation of endocannabinoid production, which then feed back on glutamate and GABA release and actions in mitochondria to affect Ca²⁺ buffering and free radical formation. BDNF, in the presence of glucocorticoids, phosphorylates the GR at sites that facilitate its translocation to the cell nucleus for transcriptional actions; this effect is synergistic with the ability of glucocorticoids to promote the phosphorylation of the TrkB receptor independently of BDNF. Table 1 refers to mechanistic studies of mediators and cellular processes that are involved in the remodeling of neurons in hippocampus, amygdala, and prefrontal cortex.