141683 20240321221011.0 10.3389/fncel.2018.00112 doi pmid:29755323 pmid pmc:PMC5932345 pmc altmetric:39772273 altmetric DZNE-2020-00014 English 610 Wassouf, Zinah P:(DE-HGF)0 0 Environmental Enrichment Prevents Transcriptional Disturbances Induced by Alpha-Synuclein Overexpression. Lausanne 2018 Frontiers Research Foundation online Crossref Frontiers Media SA 2018-04-24 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1603723792_24017 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Onset and progression of neurodegenerative disorders, including synucleinopathies such as Parkinson's disease, have been associated with various environmental factors. A highly compelling association from a therapeutic point of view has been found between a physically active lifestyle and a significantly reduced risk for Parkinson's disease. Mimicking such conditions in animal models by promoting physical activity, social interactions, and novel surroundings yields in a so-called enriched environment known to enhance adult neurogenesis, increase synaptic plasticity, and decelerate neuronal loss. Yet, the genes that connect beneficial environmental cues to the genome and delay disease-related symptoms have remained largely unclear. To identify such mediator genes, we used a 2 × 2 factorial design opposing genotype and environment. Specifically, we compared wildtype to transgenic mice overexpressing human SNCA, a key gene in synucleinopathies encoding alpha-synuclein, and housed them in a standard and enriched environment from weaning to 12 months of age before profiling their hippocampal transcriptome using RNA-sequencing. Under standard environmental conditions, differentially expressed genes were overrepresented for calcium ion binding, membrane, synapse, and other Gene Ontology terms previously linked to alpha-synuclein biology. Upregulated genes were significantly enriched for genes attributed to astrocytes, microglia, and oligodendrocytes. These disturbances in gene activity were accompanied by reduced levels of several presynaptic proteins and the immediate early genes EGR1 and NURR1. Intriguingly, housing transgenic animals in the enriched environment prevented most of these perturbations in gene activity. In addition, a sustained activation specifically in transgenic animals housed in enriched conditions was observed for several immediate early genes including Egr1, Nr4a2/Nurr1, Arc, and Homer1a. These findings suggest a compensatory mechanism through an enriched environment-activated immediate early gene network that prevented most disturbances induced by alpha-synuclein overexpression. This regulatory framework might harbor attractive targets for novel therapeutic approaches that mimic beneficial environmental stimuli. 899H - Addenda (POF3-899H) G:(DE-HGF)POF3-899H POF3-899H POF III 0 2018-04-24 Crossref https://creativecommons.org/licenses/by/4.0/ Dataset connected to CrossRef, PubMed, Hentrich, Thomas 1 Samer, Sebastian 2 Rotermund, Carola P:(DE-2719)2630394 3 dzne Kahle, Philipp J P:(DE-2719)2810803 4 dzne Ehrlich, Ingrid 5 Riess, Olaf 6 Casadei, Nicolas 7 Schulze-Hentrich, Julia M P:(DE-HGF)0 8 Corresponding author 10.3389/fncel.2018.00112 : Frontiers Media SA, 2018-04-24 journal-article Crossref Frontiers in Cellular Neuroscience 12 2018 1662-5102 10.3389/fncel.2018.00112 Vol. 12, p. 112 PERI:(DE-600)2452963-1 112 Frontiers in cellular neuroscience 12 2018 1662-5102 OpenAccess http://pub.dzne.de/record/141683/files/fncel-12-00112.pdf OpenAccess icon http://pub.dzne.de/record/141683/files/fncel-12-00112.gif?subformat=icon OpenAccess icon-1440 http://pub.dzne.de/record/141683/files/fncel-12-00112.jpg?subformat=icon-1440 OpenAccess icon-180 http://pub.dzne.de/record/141683/files/fncel-12-00112.jpg?subformat=icon-180 OpenAccess icon-640 http://pub.dzne.de/record/141683/files/fncel-12-00112.jpg?subformat=icon-640 OpenAccess pdfa http://pub.dzne.de/record/141683/files/fncel-12-00112.pdf?subformat=pdfa oai:pub.dzne.de:141683 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2630394 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 4 P:(DE-2719)2810803 DE-HGF Programmungebundene Forschung ohne Programm G:(DE-HGF)POF3-890 G:(DE-HGF)POF3-899H G:(DE-HGF)POF3-800 Addenda 0 2018 Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ OpenAccess StatID:(DE-HGF)0510 StatID JCR StatID:(DE-HGF)0100 StatID FRONT CELL NEUROSCI : 2021 2022-11-25 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-25 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-25 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2021-05-13T10:30:24Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2021-05-13T10:30:24Z Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Blind peer review 2021-05-13T10:30:24Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-25 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-25 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-25 DBCoverage StatID:(DE-HGF)1040 StatID Zoological Record 2022-11-25 IF >= 5 StatID:(DE-HGF)9905 StatID FRONT CELL NEUROSCI : 2021 2022-11-25 I:(DE-2719)1210000-4 AG Kahle 2 Functional Neurogenetics 0 journal VDB UNRESTRICTED I:(DE-2719)1210000-4 FullTexts -- missing cx lookup -- 10.1111/j.1471-4159.2009.06001.x Crossref 10.1111/j.1471-4159.2009.06001.x -- missing cx lookup -- 10.1158/0008-5472.CAN-04-0496 Crossref 10.1158/0008-5472.CAN-04-0496 Crossref -- missing cx lookup -- 10.1016/S1474-4422(16)30230-7 Crossref 10.1016/S1474-4422(16)30230-7 -- missing cx lookup -- 10.1038/nn.4201 Crossref 10.1038/nn.4201 -- missing cx lookup -- 10.1016/j.parkreldis.2015.12.008 Crossref 10.1016/j.parkreldis.2015.12.008 -- missing cx lookup -- 10.1523/JNEUROSCI.23-35-10999.2003 Crossref 10.1523/JNEUROSCI.23-35-10999.2003 -- missing cx lookup -- 10.1038/nbt.3519 Crossref 10.1038/nbt.3519 -- missing cx lookup -- 10.1016/S0140-6736(04)17103-1 Crossref 10.1016/S0140-6736(04)17103-1 -- missing cx lookup -- 10.1016/S1474-4422(06)70373-8 Crossref 10.1016/S1474-4422(06)70373-8 -- missing cx lookup -- 10.1002/cne.10261 Crossref 10.1002/cne.10261 -- missing cx lookup -- 10.1523/JNEUROSCI.2617-07.2007 Crossref 10.1523/JNEUROSCI.2617-07.2007 -- missing cx lookup -- 10.1038/nrneurol.2013.209 Crossref 10.1038/nrneurol.2013.209 -- missing cx lookup -- 10.1523/JNEUROSCI.23-12-05219.2003 Crossref 10.1523/JNEUROSCI.23-12-05219.2003 -- missing cx lookup -- 10.1093/bioinformatics/bts635 Crossref 10.1093/bioinformatics/bts635 -- missing cx lookup -- 10.1016/S0896-6273(03)00684-6 Crossref 10.1016/S0896-6273(03)00684-6 -- missing cx lookup -- 10.1016/j.molbrainres.2004.08.008 Crossref 10.1016/j.molbrainres.2004.08.008 -- missing cx lookup -- 10.1016/j.nlm.2009.01.010 Crossref 10.1016/j.nlm.2009.01.010 -- missing cx lookup -- 10.1016/j.neuroscience.2010.09.062 Crossref 10.1016/j.neuroscience.2010.09.062 -- missing cx lookup -- 10.1016/j.neuron.2008.09.002 Crossref 10.1016/j.neuron.2008.09.002 -- missing cx lookup -- 10.1038/nn.4194 Crossref 10.1038/nn.4194 -- missing cx lookup -- 10.1002/mds.23455 Crossref 10.1002/mds.23455 -- missing cx lookup -- 10.1186/gb-2007-8-2-r19 Crossref 10.1186/gb-2007-8-2-r19 -- missing cx lookup -- 10.1126/science.aad8373 Crossref 10.1126/science.aad8373 -- missing cx lookup -- 10.1007/s00401-012-1013-5 Crossref 10.1007/s00401-012-1013-5 -- missing cx lookup -- 10.1016/j.neuron.2010.11.008 Crossref 10.1016/j.neuron.2010.11.008 -- missing cx lookup -- 10.1038/nprot.2008.211 Crossref 10.1038/nprot.2008.211 -- missing cx lookup -- 10.3389/fnmol.2016.00062 Crossref 10.3389/fnmol.2016.00062 -- missing cx lookup -- 10.1038/nrn2755 Crossref 10.1038/nrn2755 -- missing cx lookup -- 10.1016/j.neuroscience.2006.03.027 Crossref 10.1016/j.neuroscience.2006.03.027 -- missing cx lookup -- 10.1016/j.expneurol.2004.08.035 Crossref 10.1016/j.expneurol.2004.08.035 -- missing cx lookup -- 10.3390/ijms18020406 Crossref 10.3390/ijms18020406 -- missing cx lookup -- 10.1038/386493a0 Crossref 10.1038/386493a0 -- missing cx lookup -- 10.1186/1471-2202-13-132 Crossref 10.1186/1471-2202-13-132 -- missing cx lookup -- 10.1016/j.pneurobio.2004.05.007 Crossref 10.1016/j.pneurobio.2004.05.007 -- missing cx lookup -- 10.1016/j.nbd.2013.11.005 Crossref 10.1016/j.nbd.2013.11.005 -- missing cx lookup -- 10.1016/j.tins.2011.08.007 Crossref 10.1016/j.tins.2011.08.007 -- missing cx lookup -- 10.1038/nrn3406 Crossref 10.1038/nrn3406 -- missing cx lookup -- 10.1523/JNEUROSCI.16-23-07428.1996 Crossref 10.1523/JNEUROSCI.16-23-07428.1996 -- missing cx lookup -- 10.1016/j.cell.2005.01.015 Crossref 10.1016/j.cell.2005.01.015 -- missing cx lookup -- 10.1093/bioinformatics/bts034 Crossref 10.1093/bioinformatics/bts034 -- missing cx lookup -- 10.1093/bioinformatics/btp352 Crossref 10.1093/bioinformatics/btp352 -- missing cx lookup -- 10.1038/nature21029 Crossref 10.1038/nature21029 -- missing cx lookup -- 10.1152/physrev.00013.2009 Crossref 10.1152/physrev.00013.2009 -- missing cx lookup -- 10.1186/s13059-014-0550-8 Crossref 10.1186/s13059-014-0550-8 -- missing cx lookup -- 10.1016/S0018-506X(03)00002-3 Crossref 10.1016/S0018-506X(03)00002-3 -- missing cx lookup -- 10.1038/nn.3816 Crossref 10.1038/nn.3816 -- missing cx lookup -- 10.3389/fnmol.2015.00078 Crossref 10.3389/fnmol.2015.00078 -- missing cx lookup -- 10.1007/s00401-007-0309-3 Crossref 10.1007/s00401-007-0309-3 -- missing cx lookup -- 10.1038/ncb898 Crossref 10.1038/ncb898 -- missing cx lookup -- 10.1038/nrn1970 Crossref 10.1038/nrn1970 -- missing cx lookup -- 10.1093/brain/aws358 Crossref 10.1093/brain/aws358 -- missing cx lookup -- 10.1038/nmeth.4197 Crossref 10.1038/nmeth.4197 -- missing cx lookup -- 10.1093/nar/29.9.e45 Crossref 10.1093/nar/29.9.e45 -- missing cx lookup -- 10.1023/B:BILE.0000019559.84305.47 Crossref 10.1023/B:BILE.0000019559.84305.47 -- missing cx lookup -- 10.1080/00207450490264142 Crossref 10.1080/00207450490264142 -- missing cx lookup -- 10.1016/j.tins.2007.03.012 Crossref 10.1016/j.tins.2007.03.012 -- missing cx lookup -- 10.1016/j.cell.2009.01.038 Crossref 10.1016/j.cell.2009.01.038 -- missing cx lookup -- 10.1093/brain/awt180 Crossref 10.1093/brain/awt180 -- missing cx lookup -- 10.1523/JNEUROSCI.22-13-05606.2002 Crossref 10.1523/JNEUROSCI.22-13-05606.2002 -- missing cx lookup -- 10.1002/mds.26620 Crossref 10.1002/mds.26620 -- missing cx lookup -- 10.1038/ng.487 Crossref 10.1038/ng.487 -- missing cx lookup -- 10.1093/brain/awn323 Crossref 10.1093/brain/awn323 -- missing cx lookup -- 10.1038/42166 Crossref 10.1038/42166 -- missing cx lookup -- 10.1038/ncomms11295 Crossref 10.1038/ncomms11295 -- missing cx lookup -- 10.1016/j.expneurol.2005.11.004 Crossref 10.1016/j.expneurol.2005.11.004 -- missing cx lookup -- 10.1016/j.febslet.2006.09.007 Crossref 10.1016/j.febslet.2006.09.007 -- missing cx lookup -- 10.1002/biof.1035 Crossref 10.1002/biof.1035 -- missing cx lookup -- 10.1093/bib/bbs017 Crossref 10.1093/bib/bbs017 -- missing cx lookup -- 10.1186/gb-2002-3-7-research0034 Crossref 10.1186/gb-2002-3-7-research0034 -- missing cx lookup -- 10.1038/35044558 Crossref 10.1038/35044558 -- missing cx lookup -- 10.1093/nar/gkt439 Crossref 10.1093/nar/gkt439 -- missing cx lookup -- 10.1186/s40035-015-0042-0 Crossref 10.1186/s40035-015-0042-0 -- missing cx lookup -- 10.1093/nar/gkq537 Crossref 10.1093/nar/gkq537 -- missing cx lookup -- 10.1016/0896-6273(93)90192-T Crossref 10.1016/0896-6273(93)90192-T -- missing cx lookup -- 10.1016/j.neures.2012.03.010 Crossref 10.1016/j.neures.2012.03.010 -- missing cx lookup -- 10.1093/brain/awu323 Crossref 10.1093/brain/awu323 -- missing cx lookup -- 10.3969/j.issn.1673-5374.2012.23.006 Crossref 10.3969/j.issn.1673-5374.2012.23.006 -- missing cx lookup -- 10.1093/nar/gkp464 Crossref 10.1093/nar/gkp464 -- missing cx lookup -- 10.1126/science.aaa1934 Crossref 10.1126/science.aaa1934