Fig. 5.

Hypothetical model illustrating possible molecular mechanisms underlying the action of the glucocorticoid receptor in the excitation-inhibition balance in NPCs. Activation of NMDA and AMPA receptors lead to an intracellular signaling cascade leading to the activation of the pro-neurogenic transcription factors CREB and zif68/EGR via CaMK. Likewise, binding of neurotrophins (e.g., BDNF) to Trks leads to activation of CREB and zif68/egr1 via the MAPK pathway. CORT-activated GR is retrograde transported by doublecortin-like (DCL) along the microtubules towards the nucleus. GR may interact with p-CREB by interaction with co-factors such as CREB binding protein (CPB). The net result of this GR-CPB-CREB interaction is the decreased CREB activity and subsequent inhibition of neurogenesis. Pro-neurogenic miR-124 represses GR activity, which may facilitate neuronal differentiation via NMDAR and/or Trk activation