Caldesmon, an actin-linked regulatory protein, comes across glucocorticoids.

The glucocorticoids (GCs), the most downstream effectors of the hypothalamic-pituitary-adrenal (HPA) axis, are the main mediators of stress response. Stress-triggered GCs as well as acute and chronic GC treatment can impair the structural plasticity and function of the brain. The exposure of perinatal animals and humans to excess stress or GCs can affect the brain development, resulting in altered behaviors in the adult offspring of animals and an increased risk of psychiatric disorders in humans. Despite the numerous studies documenting these effects, the underlying mechanism remains unclear. In this commentary we will focus on the effect of excess GCs on cortical development. We have recently showed that excess-GC-dependent retardation of the radial migration of neural progenitor cells (NPCs) is caused by the dysregulation of actin-myosin interaction via upregulation of caldesmon (CaD), an actin-linked regulatory protein. The elucidation of the molecular mechanisms that underlie the detrimental action of GCs on cortical development will expand our understanding of how stress/GCs alter the formation of neural networks and affect behaviors later in life.