000141683 001__ 141683
000141683 005__ 20240321221011.0
000141683 0247_ $$2doi$$a10.3389/fncel.2018.00112
000141683 0247_ $$2pmid$$apmid:29755323
000141683 0247_ $$2pmc$$apmc:PMC5932345
000141683 0247_ $$2altmetric$$aaltmetric:39772273
000141683 037__ $$aDZNE-2020-00014
000141683 041__ $$aEnglish
000141683 082__ $$a610
000141683 1001_ $$0P:(DE-HGF)0$$aWassouf, Zinah$$b0
000141683 245__ $$aEnvironmental Enrichment Prevents Transcriptional Disturbances Induced by Alpha-Synuclein Overexpression.
000141683 260__ $$aLausanne$$bFrontiers Research Foundation$$c2018
000141683 264_1 $$2Crossref$$3online$$bFrontiers Media SA$$c2018-04-24
000141683 3367_ $$2DRIVER$$aarticle
000141683 3367_ $$2DataCite$$aOutput Types/Journal article
000141683 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1603723792_24017
000141683 3367_ $$2BibTeX$$aARTICLE
000141683 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000141683 3367_ $$00$$2EndNote$$aJournal Article
000141683 520__ $$aOnset 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.
000141683 536__ $$0G:(DE-HGF)POF3-899H$$a899H - Addenda (POF3-899H)$$cPOF3-899H$$fPOF III$$x0
000141683 542__ $$2Crossref$$i2018-04-24$$uhttps://creativecommons.org/licenses/by/4.0/
000141683 588__ $$aDataset connected to CrossRef, PubMed,
000141683 7001_ $$aHentrich, Thomas$$b1
000141683 7001_ $$aSamer, Sebastian$$b2
000141683 7001_ $$0P:(DE-2719)2630394$$aRotermund, Carola$$b3$$udzne
000141683 7001_ $$0P:(DE-2719)2810803$$aKahle, Philipp J$$b4$$udzne
000141683 7001_ $$aEhrlich, Ingrid$$b5
000141683 7001_ $$aRiess, Olaf$$b6
000141683 7001_ $$aCasadei, Nicolas$$b7
000141683 7001_ $$0P:(DE-HGF)0$$aSchulze-Hentrich, Julia M$$b8$$eCorresponding author
000141683 77318 $$2Crossref$$3journal-article$$a10.3389/fncel.2018.00112$$b : Frontiers Media SA, 2018-04-24$$tFrontiers in Cellular Neuroscience$$v12$$x1662-5102$$y2018
000141683 773__ $$0PERI:(DE-600)2452963-1$$a10.3389/fncel.2018.00112$$gVol. 12, p. 112$$p112$$tFrontiers in cellular neuroscience$$v12$$x1662-5102$$y2018
000141683 8564_ $$uhttps://pub.dzne.de/record/141683/files/fncel-12-00112.pdf$$yOpenAccess
000141683 8564_ $$uhttps://pub.dzne.de/record/141683/files/fncel-12-00112.gif?subformat=icon$$xicon$$yOpenAccess
000141683 8564_ $$uhttps://pub.dzne.de/record/141683/files/fncel-12-00112.jpg?subformat=icon-1440$$xicon-1440$$yOpenAccess
000141683 8564_ $$uhttps://pub.dzne.de/record/141683/files/fncel-12-00112.jpg?subformat=icon-180$$xicon-180$$yOpenAccess
000141683 8564_ $$uhttps://pub.dzne.de/record/141683/files/fncel-12-00112.jpg?subformat=icon-640$$xicon-640$$yOpenAccess
000141683 8564_ $$uhttps://pub.dzne.de/record/141683/files/fncel-12-00112.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000141683 909CO $$ooai:pub.dzne.de:141683$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000141683 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2630394$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE
000141683 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810803$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b4$$kDZNE
000141683 9131_ $$0G:(DE-HGF)POF3-899H$$1G:(DE-HGF)POF3-890$$2G:(DE-HGF)POF3-800$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vAddenda$$x0
000141683 9141_ $$y2018
000141683 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ
000141683 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000141683 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bFRONT CELL NEUROSCI : 2021$$d2022-11-25
000141683 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-25
000141683 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-25
000141683 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2021-05-13T10:30:24Z
000141683 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2021-05-13T10:30:24Z
000141683 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Blind peer review$$d2021-05-13T10:30:24Z
000141683 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-25
000141683 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-25
000141683 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-25
000141683 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record$$d2022-11-25
000141683 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bFRONT CELL NEUROSCI : 2021$$d2022-11-25
000141683 9201_ $$0I:(DE-2719)1210000-4$$kAG Kahle 2$$lFunctional Neurogenetics$$x0
000141683 980__ $$ajournal
000141683 980__ $$aVDB
000141683 980__ $$aUNRESTRICTED
000141683 980__ $$aI:(DE-2719)1210000-4
000141683 9801_ $$aFullTexts
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1111/j.1471-4159.2009.06001.x$$o10.1111/j.1471-4159.2009.06001.x
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1158/0008-5472.CAN-04-0496$$o10.1158/0008-5472.CAN-04-0496
000141683 999C5 $$2Crossref$$o
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S1474-4422(16)30230-7$$o10.1016/S1474-4422(16)30230-7
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nn.4201$$o10.1038/nn.4201
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.parkreldis.2015.12.008$$o10.1016/j.parkreldis.2015.12.008
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.23-35-10999.2003$$o10.1523/JNEUROSCI.23-35-10999.2003
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nbt.3519$$o10.1038/nbt.3519
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S0140-6736(04)17103-1$$o10.1016/S0140-6736(04)17103-1
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S1474-4422(06)70373-8$$o10.1016/S1474-4422(06)70373-8
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/cne.10261$$o10.1002/cne.10261
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.2617-07.2007$$o10.1523/JNEUROSCI.2617-07.2007
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrneurol.2013.209$$o10.1038/nrneurol.2013.209
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.23-12-05219.2003$$o10.1523/JNEUROSCI.23-12-05219.2003
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/bioinformatics/bts635$$o10.1093/bioinformatics/bts635
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S0896-6273(03)00684-6$$o10.1016/S0896-6273(03)00684-6
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.molbrainres.2004.08.008$$o10.1016/j.molbrainres.2004.08.008
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.nlm.2009.01.010$$o10.1016/j.nlm.2009.01.010
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuroscience.2010.09.062$$o10.1016/j.neuroscience.2010.09.062
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuron.2008.09.002$$o10.1016/j.neuron.2008.09.002
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nn.4194$$o10.1038/nn.4194
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/mds.23455$$o10.1002/mds.23455
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/gb-2007-8-2-r19$$o10.1186/gb-2007-8-2-r19
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.aad8373$$o10.1126/science.aad8373
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-012-1013-5$$o10.1007/s00401-012-1013-5
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuron.2010.11.008$$o10.1016/j.neuron.2010.11.008
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nprot.2008.211$$o10.1038/nprot.2008.211
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3389/fnmol.2016.00062$$o10.3389/fnmol.2016.00062
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrn2755$$o10.1038/nrn2755
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neuroscience.2006.03.027$$o10.1016/j.neuroscience.2006.03.027
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.expneurol.2004.08.035$$o10.1016/j.expneurol.2004.08.035
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3390/ijms18020406$$o10.3390/ijms18020406
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/386493a0$$o10.1038/386493a0
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/1471-2202-13-132$$o10.1186/1471-2202-13-132
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.pneurobio.2004.05.007$$o10.1016/j.pneurobio.2004.05.007
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.nbd.2013.11.005$$o10.1016/j.nbd.2013.11.005
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.tins.2011.08.007$$o10.1016/j.tins.2011.08.007
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrn3406$$o10.1038/nrn3406
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.16-23-07428.1996$$o10.1523/JNEUROSCI.16-23-07428.1996
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.cell.2005.01.015$$o10.1016/j.cell.2005.01.015
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/bioinformatics/bts034$$o10.1093/bioinformatics/bts034
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/bioinformatics/btp352$$o10.1093/bioinformatics/btp352
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nature21029$$o10.1038/nature21029
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1152/physrev.00013.2009$$o10.1152/physrev.00013.2009
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/s13059-014-0550-8$$o10.1186/s13059-014-0550-8
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/S0018-506X(03)00002-3$$o10.1016/S0018-506X(03)00002-3
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nn.3816$$o10.1038/nn.3816
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3389/fnmol.2015.00078$$o10.3389/fnmol.2015.00078
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1007/s00401-007-0309-3$$o10.1007/s00401-007-0309-3
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ncb898$$o10.1038/ncb898
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nrn1970$$o10.1038/nrn1970
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/aws358$$o10.1093/brain/aws358
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/nmeth.4197$$o10.1038/nmeth.4197
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/29.9.e45$$o10.1093/nar/29.9.e45
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1023/B:BILE.0000019559.84305.47$$o10.1023/B:BILE.0000019559.84305.47
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1080/00207450490264142$$o10.1080/00207450490264142
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.tins.2007.03.012$$o10.1016/j.tins.2007.03.012
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.cell.2009.01.038$$o10.1016/j.cell.2009.01.038
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awt180$$o10.1093/brain/awt180
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1523/JNEUROSCI.22-13-05606.2002$$o10.1523/JNEUROSCI.22-13-05606.2002
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/mds.26620$$o10.1002/mds.26620
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ng.487$$o10.1038/ng.487
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awn323$$o10.1093/brain/awn323
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/42166$$o10.1038/42166
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/ncomms11295$$o10.1038/ncomms11295
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.expneurol.2005.11.004$$o10.1016/j.expneurol.2005.11.004
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.febslet.2006.09.007$$o10.1016/j.febslet.2006.09.007
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1002/biof.1035$$o10.1002/biof.1035
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/bib/bbs017$$o10.1093/bib/bbs017
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/gb-2002-3-7-research0034$$o10.1186/gb-2002-3-7-research0034
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1038/35044558$$o10.1038/35044558
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gkt439$$o10.1093/nar/gkt439
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1186/s40035-015-0042-0$$o10.1186/s40035-015-0042-0
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gkq537$$o10.1093/nar/gkq537
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/0896-6273(93)90192-T$$o10.1016/0896-6273(93)90192-T
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1016/j.neures.2012.03.010$$o10.1016/j.neures.2012.03.010
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/brain/awu323$$o10.1093/brain/awu323
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.3969/j.issn.1673-5374.2012.23.006$$o10.3969/j.issn.1673-5374.2012.23.006
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1093/nar/gkp464$$o10.1093/nar/gkp464
000141683 999C5 $$2Crossref$$9-- missing cx lookup --$$a10.1126/science.aaa1934$$o10.1126/science.aaa1934