@article{CoxLimpensVlesvandenHoveetal.2014,
  author    = {Cox-Limpens, Kimberly E. M. and Vles, Johan S. H. and van den Hove, Daniel L. A. and Zimmermann, Luc Ji and Gavilanes, Antonio W. D.},
  title     = {Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia},
  series = {BMC Neuroscience},
  volume    = {15},
  journal   = {BMC Neuroscience},
  doi       = {10.1186/1471-2202-15-67},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116185},
  pages     = {67},
  year      = {2014},
  abstract  = {Background: Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of brain preconditioning. Unraveling mechanisms of this endogenous neuroprotection, activated by preconditioning, is an important step towards new clinical strategies for treating asphyctic neonates. Therefore, we investigated whole-genome transcriptional changes in the brain of rats which underwent perinatal asphyxia (PA), and rats where PA was preceded by fetal asphyctic preconditioning (FAPA). Offspring were sacrificed 6 h and 96 h after birth, and whole-genome transcription was investigated using the Affymetrix Gene1.0ST chip. Microarray data were analyzed with the Bioconductor Limma package. In addition to univariate analysis, we performed Gene Set Enrichment Analysis (GSEA) in order to derive results with maximum biological relevance. Results: We observed minimal, 25\% or less, overlap of differentially regulated transcripts across different experimental groups which leads us to conclude that the transcriptional phenotype of these groups is largely unique. In both the PA and FAPA group we observe an upregulation of transcripts involved in cellular stress. Contrastingly, transcripts with a function in the cell nucleus were mostly downregulated in PA animals, while we see considerable upregulation in the FAPA group. Furthermore, we observed that histone deacetylases (HDACs) are exclusively regulated in FAPA animals. Conclusions: This study is the first to investigate whole-genome transcription in the neonatal brain after PA alone, and after perinatal asphyxia preceded by preconditioning (FAPA). We describe several genes/pathways, such as ubiquitination and proteolysis, which were not previously linked to preconditioning-induced neuroprotection. Furthermore, we observed that the majority of upregulated genes in preconditioned animals have a function in the cell nucleus, including several epigenetic players such as HDACs, which suggests that epigenetic mechanisms are likely to play a role in preconditioning-induced neuroprotection.},
  language  = {en}
}
@article{SchaefferKuehnSchmittetal.2013,
  author    = {Schaeffer, Evelin L. and K{\"u}hn, Franziska and Schmitt, Angelika and Gattaz, Wagner F. and Gruber, Oliver and Schneider-Axmann, Thomas and Falkai, Peter and Schmitt, Andrea},
  title     = {Increased cell proliferation in the rat anterior cingulate cortex following neonatal hypoxia: relevance to schizophrenia},
  series = {Journal of Neural Transmission},
  volume    = {120},
  journal   = {Journal of Neural Transmission},
  number    = {1},
  doi       = {10.1007/s00702-012-0859-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125890},
  pages     = {187-195},
  year      = {2013},
  abstract  = {As a consequence of obstetric complications, neonatal hypoxia has been discussed as an environmental factor in the pathophysiology of schizophrenia. However, the biological consequences of hypoxia are unclear. The neurodevelopmental hypothesis of schizophrenia suggests that the onset of abnormal brain development and neuropathology occurs perinatally, whereas symptoms of the disease appear in early adulthood. In our animal model of chronic neonatal hypoxia, we have detected behavioral alterations resembling those known from schizophrenia. Disturbances in cell proliferation possibly contribute to the pathophysiology of this disease. In the present study, we used postnatal rats to investigate cell proliferation in several brain areas following neonatal hypoxia. Rats were repeatedly exposed to hypoxia (89 \% N2, 11 \% O2) from postnatal day (PD) 4-8. We then evaluated cell proliferation on PD 13 and 39, respectively. These investigations were performed in the anterior cingulate cortex (ACC), caudate-putamen (CPU), dentate gyrus, and subventricular zone. Rats exposed to hypoxia exhibited increased cell proliferation in the ACC at PD 13, normalizing at PD 39. In other brain regions, no alterations have been detected. Additionally, hypoxia-treated rats showed decreased CPU volume at PD 13. The results of the present study on the one hand support the assumption of chronic hypoxia influencing transient cell proliferation in the ACC, and on the other hand reveal normalization during ageing.},
  language  = {en}
}