EURON and THEME joint PhD meeting
EURON and THEME joint PhD meeting
EURON and THEME joint PhD meeting
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47<br />
<strong>EURON</strong> <strong>and</strong> <strong>THEME</strong> <strong>joint</strong> <strong>meeting</strong> 2011<br />
Neurogenomics in perinatal asphyxia <strong>and</strong> fetal<br />
preconditioning<br />
KEM Cox, E Strackx, E Vlassaks, M Sparnaaij, L Zimmerman, JS Vles, AW Gavilanes.<br />
Dept of Psychiatry <strong>and</strong> Neuropsychology, Maastricht University, The Netherl<strong>and</strong>s.<br />
Background<br />
Part of perinatal hypoxic-ischemic brain damage can be attenuated when it is<br />
preceded by fetal preconditioning. The mechanism behind this endogenous<br />
neuroprotective phenomenon has not been deciphered yet. It is suggested that<br />
genomic reprogramming could be the answer to this question. We performed<br />
50 micro array experiments to evaluate changes in cerebral gene expression<br />
after fetal preconditioning <strong>and</strong> perinatal asphyxia at multiple time points. In this<br />
abstract we describe some preliminary results.<br />
Objective<br />
We aim to analyze the whole genome gene expression at multiple time points<br />
in pre- <strong>and</strong> neonatal pups after fetal preconditioning (FA) <strong>and</strong> perinatal asphyxia<br />
(PA). This can give us insight into the mechanisms of endogenous neuroprotection<br />
after FA <strong>and</strong> the deleterious effects of PA. Unraveling these mechanisms is an<br />
important step towards possible new clinical strategies for asphyctic neonates.<br />
Design/Methods<br />
FA was induced on E17 by clamping the uterine circulation of the maternal rat for<br />
30 minutes. On P0 pups PA was induced by placing the uterine horns, including<br />
the fetuses, in a water bath for 19 minutes. Control (CCD) <strong>and</strong> FA pups were<br />
delivered by Caesarean section. These procedures generated four experimental<br />
groups: CCD, FA, PA, <strong>and</strong> FA+PA. Five male pups per group were sacrificed at the<br />
following time points: 96h after FA, 6h <strong>and</strong> 96h after birth. RNA was isolated from<br />
the left hemispheres <strong>and</strong> 50 micro array experiments were performed on the<br />
Affymetrix platform. Up- or down-regulation of gene-products was studied via<br />
Gene-Ontology terms with a computational method named Gene Set Enrichment<br />
Analysis (GSEA).<br />
Results<br />
With GSEA we found a considerable number of GO-terms that were significantly<br />
up- or down-regulated compared to CCD animals (see figure 1). Interestingly in<br />
the protected phenotype (FA+PA) no GO-terms were significantly different from<br />
the control phenotype 6 hours after birth. Four days after perinatal asphyxia we
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