@article{VandenHoveJakobSchrautetal.2011, author = {Van den Hove, Daniel and Jakob, Sissi Brigitte and Schraut, Karla-Gerlinde and Kenis, Gunter and Schmitt, Angelika Gertrud and Kneitz, Susanne and Scholz, Claus-J{\"u}rgen and Wiescholleck, Valentina and Ortega, Gabriela and Prickaerts, Jos and Steinbusch, Harry and Lesch, Klaus-Peter}, title = {Differential Effects of Prenatal Stress in 5-Htt Deficient Mice: Towards Molecular Mechanisms of Gene x Environment Interactions}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75795}, year = {2011}, abstract = {Prenatal stress (PS) has been shown to influence the development of the fetal brain and to increase the risk for the development of psychiatric disorders in later life. Furthermore, the variation of human serotonin transporter (5-HTT, SLC6A4) gene was suggested to exert a modulating effect on the association between early life stress and the risk for depression. In the present study, we used a 5-Htt6PS paradigm to investigate whether the effects of PS are dependent on the 5-Htt genotype. For this purpose, the effects of PS on cognition, anxiety- and depression-related behavior were examined using a maternal restraint stress paradigm of PS in C57BL6 wild-type (WT) and heterozygous 5-Htt deficient (5-Htt +/2) mice. Additionally, in female offspring, a genome-wide hippocampal gene expression profiling was performed using the Affymetrix GeneChipH Mouse Genome 430 2.0 Array. 5-Htt +/2 offspring showed enhanced memory performance and signs of reduced anxiety as compared to WT offspring. In contrast, exposure of 5-Htt +/2 mice to PS was associated with increased depressive-like behavior, an effect that tended to be more pronounced in female offspring. Further, 5-Htt genotype, PS and their interaction differentially affected the expression of numerous genes and related pathways within the female hippocampus. Specifically, MAPK and neurotrophin signaling were regulated by both the 5-Htt +/2 genotype and PS exposure, whereas cytokine and Wnt signaling were affected in a 5-Htt genotype6PS manner, indicating a gene6environment interaction at the molecular level. In conclusion, our data suggest that although the 5-Htt +/2 genotype shows clear adaptive capacity, 5-Htt +/2 mice -particularly females- at the same time appear to be more vulnerable to developmental stress exposure when compared to WT offspring. Moreover, hippocampal gene expression profiles suggest that distinct molecular mechanisms mediate the behavioral effects of the 5-Htt genotype, PS exposure, and their interaction.}, subject = {Medizin}, language = {en} } @article{VandenHoveJakobSchrautetal.2011, author = {Van den Hove, Daniel and Jakob, Sissi Brigitte and Schraut, Karla-Gerlinde and Kenis, Gunter and Schmitt, Angelika Gertrud and Kneitz, Susanne and Scholz, Claus-J{\"u}rgen and Wiescholleck, Valentina and Ortega, Gabriela and Prickaerts, Jos and Steinbusch, Harry and Lesch, Klaus-Peter}, title = {Differential Effects of Prenatal Stress in 5-Htt Deficient Mice: Towards Molecular Mechanisms of Gene x Environment Interactions}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0022715}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135111}, pages = {e22715}, year = {2011}, abstract = {Prenatal stress (PS) has been shown to influence the development of the fetal brain and to increase the risk for the development of psychiatric disorders in later life. Furthermore, the variation of human serotonin transporter (5-HTT, SLC6A4) gene was suggested to exert a modulating effect on the association between early life stress and the risk for depression. In the present study, we used a 5-HttxPS paradigm to investigate whether the effects of PS are dependent on the 5-Htt genotype. For this purpose, the effects of PS on cognition, anxiety-and depression-related behavior were examined using a maternal restraint stress paradigm of PS in C57BL6 wild-type (WT) and heterozygous 5-Htt deficient (5-Htt +/-) mice. Additionally, in female offspring, a genome-wide hippocampal gene expression profiling was performed using the Affymetrix GeneChip (R) Mouse Genome 430 2.0 Array. 5-Htt +/- offspring showed enhanced memory performance and signs of reduced anxiety as compared to WT offspring. In contrast, exposure of 5-Htt +/- mice to PS was associated with increased depressive-like behavior, an effect that tended to be more pronounced in female offspring. Further, 5-Htt genotype, PS and their interaction differentially affected the expression of numerous genes and related pathways within the female hippocampus. Specifically, MAPK and neurotrophin signaling were regulated by both the 5-Htt +/- genotype and PS exposure, whereas cytokine and Wnt signaling were affected in a 5-Htt genotypexPS manner, indicating a genexenvironment interaction at the molecular level. In conclusion, our data suggest that although the 5-Htt +/- genotype shows clear adaptive capacity, 5-Htt +/- mice -particularly females-at the same time appear to be more vulnerable to developmental stress exposure when compared to WT offspring. Moreover, hippocampal gene expression profiles suggest that distinct molecular mechanisms mediate the behavioral effects of the 5-Htt genotype, PS exposure, and their interaction.}, language = {en} } @article{TianeSchepersRombautetal.2019, author = {Tiane, Assia and Schepers, Melissa and Rombaut, Ben and Hupperts, Raymond and Prickaerts, Jos and Hellings, Niels and van den Hove, Daniel and Vanmierlo, Tim}, title = {From OPC to oligodendrocyte: an epigenetic journey}, series = {Cells}, volume = {8}, journal = {Cells}, number = {10}, issn = {2073-4409}, doi = {10.3390/cells8101236}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193267}, year = {2019}, abstract = {Oligodendrocytes provide metabolic and functional support to neuronal cells, rendering them key players in the functioning of the central nervous system. Oligodendrocytes need to be newly formed from a pool of oligodendrocyte precursor cells (OPCs). The differentiation of OPCs into mature and myelinating cells is a multistep process, tightly controlled by spatiotemporal activation and repression of specific growth and transcription factors. While oligodendrocyte turnover is rather slow under physiological conditions, a disruption in this balanced differentiation process, for example in case of a differentiation block, could have devastating consequences during ageing and in pathological conditions, such as multiple sclerosis. Over the recent years, increasing evidence has shown that epigenetic mechanisms, such as DNA methylation, histone modifications, and microRNAs, are major contributors to OPC differentiation. In this review, we discuss how these epigenetic mechanisms orchestrate and influence oligodendrocyte maturation. These insights are a crucial starting point for studies that aim to identify the contribution of epigenetics in demyelinating diseases and may thus provide new therapeutic targets to induce myelin repair in the long run.}, language = {en} } @article{KittelSchneiderKenisScheketal.2012, author = {Kittel-Schneider, Sarah and Kenis, Gunter and Schek, Julia and van den Hove, Daniel and Prickaerts, Jos and Lesch, Klaus-Peter and Steinbusch, Harry and Reif, Andreas}, title = {Expression of monoamine transporters, nitric oxide synthase 3, and neurotrophin genes in antidepressant-stimulated astrocytes}, series = {Frontiers in Psychiatry}, volume = {3}, journal = {Frontiers in Psychiatry}, doi = {10.3389/fpsyt.2012.00033}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123627}, pages = {33}, year = {2012}, abstract = {Background: There is increasing evidence that glial cells play a role in the pathomechanisms of mood disorders and the mode of action of antidepressant drugs. Methods: To examine whether there is a direct effect on the expression of different genes encoding proteins that have been implicated in the pathophysiology of affective disorders, primary astrocyte cell cultures from rats were treated with two different antidepressant drugs, imipramine and escitalopram, and the RNA expression of brain-derived neurotrophic factor (Bdnf), serotonin transporter (5Htt), dopamine transporter (Dat), and endothelial nitric oxide synthase (Nos3) was examined. Results: Stimulation of astroglial cell culture with imipramine, a tricyclic antidepressant, led to a significant increase of the Bdnf RNA level whereas treatment with escitalopram did not. In contrast, 5Htt was not differentially expressed after antidepressant treatment. Finally, neither Dat nor Nos3 RNA expression was detected in cultured astrocytes. Conclusion: These data provide further evidence for a role of astroglial cells in the molecular mechanisms of action of antidepressants.}, language = {en} }