Acute central effects of neonatal dexamethasone treatment
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1
Leiden University, LACDR/LUMC, Netherlands
Dexamethasone, a synthetic glucocorticoid, is widely used to treat severe respiratory distress syndrome in prematurely born infants. Despite the potential short-term benefits on lung function, there has been growing concern about the long-term neurodevelopmental outcome of this treatment, since follow-up studies of premature infants have shown pervasive adverse neurodevelopmental effects. Additionally, rodent studies report that neonatal treatment with dexamethasone (dex) results in a reduction in lifespan of 25%, which is accompanied by reduced growth and motor performance along with impaired cognitive performance and hippocampal function. Since the mechanisms underlying these neurodevelopmental impairments are largely unknown, the goal of this study is to investigate the acute effects of neonatal glucocorticoid treatment on the developing brain. Additionally, we aim to study the possibility to antagonize specifically the central effects of dex treatment, while leaving its peripheral action intact, by direct administration of a glucocorticoid receptor (GR) antagonist into the cerebral ventricles (ICV).
Rat pups are injected with tapering doses of dex or saline on postnatal days (pnd) 1, 2 and 3. On pnd 4 and 10 pups are sacrificed by transcardial perfusion and brains are collected for analysis of markers for cell proliferation (Ki67) and glial activity (GFAP). These animals will be compared with animals in which the brain GR is blocked prior to dex administration.
Our preliminary results show that neonatal dex affects hippocampal cell proliferation and causes a reduction in number and activity of astrocytes within different brain areas one week post treatment. This reduction is normalized by central pretreatment with the GR antagonist, suggesting that this local treatment appears to be effective in preventing certain dex-induced changes in the developing brain.
Supported by EU LifeSpan (FP6 036894) (SC), NWO-DFG:IRTG (MO), KNAW (ERdK), and SmartMix (DC)
Conference:
41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009.
Presentation Type:
Poster Presentation
Topic:
Poster presentations
Citation:
Claessens
S,
Oitzl
MS,
De Kloet
ER and
Champagne
DL
(2009). Acute central effects of neonatal dexamethasone treatment.
Conference Abstract:
41st European Brain and Behaviour Society Meeting.
doi: 10.3389/conf.neuro.08.2009.09.118
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Received:
08 Jun 2009;
Published Online:
08 Jun 2009.
*
Correspondence:
Sanne Claessens, Leiden University, LACDR/LUMC, Leiden, Netherlands, s.claessens@lacdr.leidenuniv.nl