Abstract
Glucocorticoids (GCs) play a critical role in neural development; however, their prenatal or neonatal therapeutic use can have detrimental effects on the developing brain. In this issue of the JCI, Heine and Rowitch report that the molecular mechanisms underlying these detrimental effects involve the sonic hedgehog (Shh) signaling pathway, a crucial regulator of brain development and neural stem/progenitor cells (see the related study beginning on page 267). They show that GCs suppress Shh-induced proliferation of cerebellar progenitor cells in postnatal mice and that, conversely, Shh signaling is protective against GC-induced neonatal cerebellar injury by inducing the enzyme 11?HSD2, which inactivates the GCs corticosterone and prednisolone, but not dexamethasone. The data provide a rationale for the therapeutic use of 11?HSD2-sensitive GCs, but not dexamethasone, or for the exploitation of the neuroprotective effect of Shh agonists to prevent GCinduced pre- or neonatal brain injury.
| Original language | English |
|---|---|
| Pages (from-to) | 243-246 |
| Number of pages | 4 |
| Journal | Journal of Clinical Investigation |
| Volume | 119 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2 2009 |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
Glucocorticoids and neonatal brain injury : The hedgehog connection. / Gulino, Alberto; De Smaele, Enrico; Ferretti, Elisabetta.
In: Journal of Clinical Investigation, Vol. 119, No. 2, 02.02.2009, p. 243-246.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glucocorticoids and neonatal brain injury
T2 - The hedgehog connection
AU - Gulino, Alberto
AU - De Smaele, Enrico
AU - Ferretti, Elisabetta
PY - 2009/2/2
Y1 - 2009/2/2
N2 - Glucocorticoids (GCs) play a critical role in neural development; however, their prenatal or neonatal therapeutic use can have detrimental effects on the developing brain. In this issue of the JCI, Heine and Rowitch report that the molecular mechanisms underlying these detrimental effects involve the sonic hedgehog (Shh) signaling pathway, a crucial regulator of brain development and neural stem/progenitor cells (see the related study beginning on page 267). They show that GCs suppress Shh-induced proliferation of cerebellar progenitor cells in postnatal mice and that, conversely, Shh signaling is protective against GC-induced neonatal cerebellar injury by inducing the enzyme 11?HSD2, which inactivates the GCs corticosterone and prednisolone, but not dexamethasone. The data provide a rationale for the therapeutic use of 11?HSD2-sensitive GCs, but not dexamethasone, or for the exploitation of the neuroprotective effect of Shh agonists to prevent GCinduced pre- or neonatal brain injury.
AB - Glucocorticoids (GCs) play a critical role in neural development; however, their prenatal or neonatal therapeutic use can have detrimental effects on the developing brain. In this issue of the JCI, Heine and Rowitch report that the molecular mechanisms underlying these detrimental effects involve the sonic hedgehog (Shh) signaling pathway, a crucial regulator of brain development and neural stem/progenitor cells (see the related study beginning on page 267). They show that GCs suppress Shh-induced proliferation of cerebellar progenitor cells in postnatal mice and that, conversely, Shh signaling is protective against GC-induced neonatal cerebellar injury by inducing the enzyme 11?HSD2, which inactivates the GCs corticosterone and prednisolone, but not dexamethasone. The data provide a rationale for the therapeutic use of 11?HSD2-sensitive GCs, but not dexamethasone, or for the exploitation of the neuroprotective effect of Shh agonists to prevent GCinduced pre- or neonatal brain injury.
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UR - http://www.scopus.com/inward/citedby.url?scp=61749092250&partnerID=8YFLogxK
U2 - 10.1172/JCI38387
DO - 10.1172/JCI38387
M3 - Article
C2 - 19244604
AN - SCOPUS:61749092250
VL - 119
SP - 243
EP - 246
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 2
ER -