Are BDNF and glucocorticoid activities calibrated?

One hypothesis to account for the onset and severity of neurological disorders is the loss of trophic support. Indeed, changes in the levels and activities of brain-derived neurotrophic factor (BDNF) occur in numerous neurodegenerative and neuropsychiatric diseases. A deficit promotes vulnerability whereas a gain of function facilitates recovery by enhancing survival, synapse formation and synaptic plasticity. Implementation of ‘BDNF therapies’, however, faces numerous methodological and pharmacokinetic issues. Identifying BDNF mimetics that activate the BDNF receptor or downstream targets of BDNF signaling represent an alternative approach. One mechanism that shows great promise is to study the interplay of BDNF and glucocorticoid hormones, a major class of natural steroid secreted during stress reactions and in synchrony with circadian rhythms. While small amounts of glucocorticoids support normal brain function, excess stimulation by these steroid hormones precipitates stress-related affective disorders. To date, however, because of the paucity of knowledge of underlying cellular mechanisms, deleterious effects of glucocorticoids are not prevented following extreme stress. In the present review, we will discuss the complementary roles shared by BDNF and glucocorticoids in synaptic plasticity, and delineate possible signaling mechanisms mediating these effects.

The schematic is modified from Martin and Finsterwald (Commun Integr Biol. 4, 14–16, 2011).Figure optionsDownload high-quality image (228 K)Download as PowerPoint slideHighlights
• Glucocorticoid oscillations enhance dendritic spine plasticity.
• Disruption of glucocorticoid rhythms precipitates neurological disorders.
• Normalization of glucocorticoid rhythms is possible with antidepressants.
• BDNF mediates the effects of antidepressants.
• Are BDNF and glucocorticoid activities calibrated?