[Interaction of glucocorticoids and the Sonic Hedgehog pathway during brain development]

Abstract

Corticosteroids have been used for the past 20-30 years to prevent lethal consequences of pulmonary and cerebral disorders linked to prematurity. However, many data suggest a low risk-benefit ratio, and the long-term emergence of adverse neurodevelopmental outcomes objectivated by RMN studies. Although multiple mechanisms have been proposed to explain GCs effects on brain development, none has clearly emerged so far. A breakthrough study has been recently published, which identified the sonic hedgehog (Shh) signaling pathway as the target of Gcs action. Shh is a crucial regulator of brain development and neural stem/progenitor cells, and GCs suppress Shh-induced proliferation of cerebellar progenitor cells ; Shh acts through the induction of the enzyme 11betaHSD2, which inactivates the GCs corticosterone and prednisolone, but not dexamethasone. These data should lead to the development of novel molecules (either GC or Shh agonists) both -efficient and neuroprotective.