[Interaction of glucocorticoids and the Sonic Hedgehog pathway during brain development].
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.
Baud
Olivier
O
AP-HP, service de Réanimation et pédiatrie néonatales, hôpital Robert Debré, 48, boulevard Sérurier, 75019 Paris, France. Inserm Avenir R05230HS, Paris, France. olivier.baud@rdb.aphp.fr
Gressens
Pierre
P
D001921:Brain / Q000254:growth & development / Q000502:physiology* / Q000503:physiopathology; D001927:Brain Diseases / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000627:therapeutic use*; D053823:Hedgehog Proteins / Q000502:physiology*; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018570:Risk Assessment
D005938:Glucocorticoids; D053823:Hedgehog Proteins; D018696:Neuroprotective Agents