Neurotrophins and glucocorticoids are strong synaptic modifiers, and deregulation of their activities is considered to be a risk factor for developing stress-related disorders. Low levels of brain-derived neurotrophic factor (BDNF) increase the desensitization of glucocorticoid receptors and vulnerability to stress, whereas higher levels of BDNF facilitate glucocorticoid receptor-mediated signaling and the response to antidepressants.

This study shows that activation of a TrkB-MAPK pathway, when paired with the deactivation of a glucocorticoid receptor-protein phosphatase 5 pathway, resulted in sustained glucocorticoid receptor phosphorylation at BDNF-sensitive sites that is essential for the transcription of neuronal plasticity genes.

Disruption of glucocorticoid receptor phosphorylation or TrkB signaling impaired the neuroplasticity to chronic stress and the effects of the antidepressant fluoxetine. The authors suggest that the coordinated actions of BDNF and glucocorticoids promote neuronal plasticity and that disruption in either pathway could facilitate development of stress-induced psychiatric diseases.
.
Arango-Lievano M, Lambert WM, Bath KG, Garabedian MJ, Chao MV and Jeanneteau F: Neurotrophic-priming of glucocorticoid receptor signaling is essential for neuronal plasticity to stress and antidepressant treatment. PNAS 112(51): 15737–15742 (2015).
.
http://www.ncbi.nlm.nih.gov/pubmed/26630005