Schütz, Anna-Lena

[["dc.contributor.author","Fischer, André"],["dc.contributor.author","Sakib, M Sadman"],["dc.contributor.author","Kerimoglu, Cemil"],["dc.contributor.author","Burkhardt, Susanne"],["dc.contributor.author","Schütz, Anna-Lena"],["dc.contributor.author","Irniger, Stefan"],["dc.contributor.author","Capece, Vincenzo"],["dc.date.accessioned","2018-04-11T16:20:54Z"],["dc.date.available","2018-04-11T16:20:54Z"],["dc.date.issued","2016"],["dc.description.abstract","Although histone modifications and DNA methylation have been meticulously studied in the context of learning & memory formation, very few studies have demonstrated non-canonical histone variants as potential regulators of memory formation. Compared to canonical histones, these histone variants are expressed independently of DNA replication and are important for many physiological events as they confer altered chromatin structures, thereby regulating transcription. Recently, H2A.Z (variant of canonical histone, H2A) has been reported as a novel epigenetic regulator in memory formation (Zovkic et. al. 2014), which raised the question, whether differential binding of H2A.Z or its modification (e.g acetylation) across the whole genome could be a stable modulator for life-long memory acquisition and cognition. Here, we investigated genomic regions bound by H2A.Z and its acetylated variant (H2A.Zac) using chromatin immunoprecipitation followed by sequencing (ChIP-seq) in FACS-sorted neuronal and nonneuronal nuclei from hippocampal CA1 region. Initially, mRNA levels of H2afz (gene of H2A.Z) were assessed in CA1 region of aged (16 months old) and Alzheimer’s model mice (5XFAD) comparing them to young (3 months old) and wild type mice respectively. Furthermore, ChIP protocols for H2A.Z and H2A.Zac were optimized, as it has not been done before in this context. As a model of enhanced cognition, hippocampal CA1 regions from mice subjected to 4 months enriched environment (EE) were used for ChIP-seq against H2A.Z and H2A.Zac, comparing to home caged animals as controls. ChIP-seq analysis showed decreased binding of H2A.Z and its de-acetylation at specific promoter regions in CA1 neurons upon environmental enrichment. Promoters with decreased binding or decreased acetylation were found to be involved in genes functionally associated with neurogenesis, synaptic plasticity and several biosynthetic pathways. Further study is needed to prove their effect on transcription of those genes."],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13225"],["dc.language.iso","en"],["dc.notes.preprint","yes"],["dc.notes.status","final"],["dc.relation.eventend","4"],["dc.relation.eventlocation","Obergurgl, Austria"],["dc.relation.eventstart","28"],["dc.relation.iserratumof","yes"],["dc.title","Differential binding of non-canonical histone variant H2A.Z & its de-acetylation is evident in enhanced cognitive function"],["dc.type","conference_paper"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3572"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","3584"],["dc.bibliographiccitation.volume","125"],["dc.contributor.author","Benito-Garagorri, Eva"],["dc.contributor.author","Urbanke, Hendrik"],["dc.contributor.author","Ramachandran, Binu"],["dc.contributor.author","Barth, Jonas"],["dc.contributor.author","Haider, Rashi"],["dc.contributor.author","Awasthi, Ankit"],["dc.contributor.author","Jain, Gaurav"],["dc.contributor.author","Capece, Vincenzo"],["dc.contributor.author","Burkhardt, Susanne"],["dc.contributor.author","Navarro-Sala, Magdalena"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Schuetz, Anna-Lena"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Luehrmann, Reinhard"],["dc.contributor.author","Dean, Camin"],["dc.contributor.author","Fischer, Andre"],["dc.date.accessioned","2017-09-07T11:43:34Z"],["dc.date.available","2017-09-07T11:43:34Z"],["dc.date.issued","2015"],["dc.description.abstract","Aging and increased amyloid burden are major risk factors for cognitive diseases such as Alzheimer's disease (AD). Effective therapies for these diseases are lacking. Here, we evaluated mouse models of age-associated memory impairment and amyloid deposition to study transcriptome and cell type-specific epigenome plasticity in the brain and peripheral organs. We determined that aging and amyloid pathology are associated with inflammation and impaired synaptic function in the hippocampal CA1 region as the result of epigenetic-dependent alterations in gene expression. In both amyloid and aging models, inflammation was associated with increased gene expression linked to a subset of transcription factors, while plasticity gene deregulation was differentially mediated. Amyloid pathology impaired histone acetylation and decreased expression of plasticity genes, while aging altered H4K12 acetylation-linked differential splicing at the intron-exon junction in neurons, but not nonneuronal cells. Furthermore, oral administration of the clinically approved histone deacetylase inhibitor vorinostat not only restored spatial memory, but also exerted antiinflammatory action and reinstated epigenetic balance and transcriptional homeostasis at the level of gene expression and exon usage. This study provides a systems-level investigation of transcriptome plasticity in the hippocampal CA1 region in aging and AD models and suggests that histone deacetylase inhibitors should be further explored as a cost-effective therapeutic strategy against age-associated cognitive decline."],["dc.identifier.doi","10.1172/JCI79942"],["dc.identifier.gro","3141833"],["dc.identifier.isi","000362303600031"],["dc.identifier.pmid","26280576"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1579"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1558-8238"],["dc.relation.issn","0021-9738"],["dc.title","HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","35"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communication"],["dc.bibliographiccitation.lastpage","20"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Fischer, Andre"],["dc.contributor.author","Thüne, Katrin"],["dc.contributor.author","Sikorska, Beata"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Tahir, Waqas"],["dc.contributor.author","Fernández-Borges, Natalia"],["dc.contributor.author","Cramm, Maria"],["dc.contributor.author","Gotzmann, Nadine"],["dc.contributor.author","Carmona, Margarita"],["dc.contributor.author","Streichenberger, Nathalie"],["dc.contributor.author","Michel, Uwe"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Schuetz, Anna-Lena"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Andréoletti, Olivier"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Liberski, Pawel P."],["dc.contributor.author","Torres, Juan Maria"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-01-09T14:57:08Z"],["dc.date.available","2018-01-09T14:57:08Z"],["dc.date.issued","2017-04-27"],["dc.description.abstract","Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human prion disease and it is characterized by the presence of neuronal loss, spongiform degeneration, chronic inflammation and the accumulation of misfolded and pathogenic prion protein (PrPSc). The molecular mechanisms underlying these alterations are largely unknown, but the presence of intracellular neuronal calcium (Ca2+) overload, a general feature in models of prion diseases, is suggested to play a key role in prion pathogenesis.Here we describe the presence of massive regulation of Ca2+ responsive genes in sCJD brain tissue, accompanied by two Ca2+-dependent processes: endoplasmic reticulum stress and the activation of the cysteine proteases Calpains 1/2. Pathogenic Calpain proteins activation in sCJD is linked to the cleavage of their cellular substrates, impaired autophagy and lysosomal damage, which is partially reversed by Calpain inhibition in a cellular prion model. Additionally, Calpain 1 treatment enhances seeding activity of PrPSc in a prion conversion assay. Neuronal lysosomal impairment caused by Calpain over activation leads to the release of the lysosomal protease Cathepsin S that in sCJD mainly localises in axons, although massive Cathepsin S overexpression is detected in microglial cells. Alterations in Ca2+ homeostasis and activation of Calpain-Cathepsin axis already occur at pre-clinical stages of the disease as detected in a humanized sCJD mouse model.Altogether our work indicates that unbalanced Calpain-Cathepsin activation is a relevant contributor to the pathogenesis of sCJD at multiple molecular levels and a potential target for therapeutic intervention."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1186/s40478-017-0431-y"],["dc.identifier.pmid","28449707"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14726"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11612"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","2051-5960"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Altered Ca2+ homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1912"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","1927"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Stilling, Roman Manuel"],["dc.contributor.author","Roenicke, Raik"],["dc.contributor.author","Benito-Garagorri, Eva"],["dc.contributor.author","Urbanke, Hendrik"],["dc.contributor.author","Capece, Vincenzo"],["dc.contributor.author","Burkhardt, Susanne"],["dc.contributor.author","Bahari-Javan, Sanaz"],["dc.contributor.author","Barth, Jonas"],["dc.contributor.author","Sananbenesi, Farahnaz"],["dc.contributor.author","Schuetz, Anna L."],["dc.contributor.author","Dyczkowski, Jerzy"],["dc.contributor.author","Martinez-Hernandez, Ana"],["dc.contributor.author","Kerimoglu, Cemil"],["dc.contributor.author","Dent, Sharon Y. R."],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Reymann, Klaus G."],["dc.contributor.author","Fischer, Andre"],["dc.date.accessioned","2017-09-07T11:45:35Z"],["dc.date.available","2017-09-07T11:45:35Z"],["dc.date.issued","2014"],["dc.description.abstract","Neuronal histone acetylation has been linked to memory consolidation, and targeting histone acetylation has emerged as a promising therapeutic strategy for neuropsychiatric diseases. However, the role of histone-modifying enzymes in the adult brain is still far from being understood. Here we use RNA sequencing to screen the levels of all known histone acetyltransferases (HATs) in the hippocampal CA1 region and find that K-acetyltransferase 2a (Kat2a)-a HAT that has not been studied for its role in memory function so far-shows highest expression. Mice that lack Kat2a show impaired hippocampal synaptic plasticity and long-term memory consolidation. We furthermore show that Kat2a regulates a highly interconnected hippocampal gene expression network linked to neuroactive receptor signaling via a mechanism that involves nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B). In conclusion, our data establish Kat2a as a novel and essential regulator of hippocampal memory consolidation."],["dc.identifier.doi","10.15252/embj.201487870"],["dc.identifier.gro","3142062"],["dc.identifier.isi","000341839500009"],["dc.identifier.pmid","25024434"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4123"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1460-2075"],["dc.relation.issn","0261-4189"],["dc.title","K-Lysine acetyltransferase 2a regulates a hippocampal gene expression network linked to memory formation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2231"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","2246"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Paiva, Isabel"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Pavlou, Maria Angeliki"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Wales, Pauline"],["dc.contributor.author","Schütz, Anna-Lena"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Szegő, Éva M."],["dc.contributor.author","Kerimoglu, Cemil"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Rego, Ana Cristina"],["dc.contributor.author","Fischer, André"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Outeiro, Tiago F."],["dc.date.accessioned","2018-04-23T11:47:17Z"],["dc.date.available","2018-04-23T11:47:17Z"],["dc.date.issued","2017"],["dc.description.abstract","Alpha-synuclein (aSyn) is considered a major culprit in Parkinson’s disease (PD) pathophysiology. However, the precise molecular function of the protein remains elusive. Recent evidence suggests that aSyn may play a role on transcription regulation, possibly by modulating the acetylation status of histones. Our study aimed at evaluating the impact of wild-type (WT) and mutant A30P aSyn on gene expression, in a dopaminergic neuronal cell model, and decipher potential mechanisms underlying aSyn-mediated transcriptional deregulation. We performed gene expression analysis using RNA-sequencing in Lund Human Mesencephalic (LUHMES) cells expressing endogenous (control) or increased levels of WT or A30P aSyn. Compared to control cells, cells expressing both aSyn variants exhibited robust changes in the expression of several genes, including downregulation of major genes involved in DNA repair. WT aSyn, unlike A30P aSyn, promoted DNA damage and increased levels of phosphorylated p53. In dopaminergic neuronal cells, increased aSyn expression led to reduced levels of acetylated histone 3. Importantly, treatment with sodium butyrate, a histone deacetylase inhibitor (HDACi), rescued WT aSyn-induced DNA damage, possibly via upregulation of genes involved in DNA repair. Overall, our findings provide novel and compelling insight into the mechanisms associated with aSyn neurotoxicity in dopaminergic cells, which could be ameliorated with an HDACi. Future studies will be crucial to further validate these findings and to define novel possible targets for intervention in PD."],["dc.identifier.doi","10.1093/hmg/ddx114"],["dc.identifier.gro","3142201"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13321"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0964-6906"],["dc.title","Sodium butyrate rescues dopaminergic cells from alpha-synuclein-induced transcriptional deregulation and DNA damage"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","102"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","110"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Halder, Rashi"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Vidal, Ramon O."],["dc.contributor.author","Shomroni, Orr"],["dc.contributor.author","Rahman, Raza-Ur"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Centeno, Tonatiuh Pena"],["dc.contributor.author","van Bebber, Frauke"],["dc.contributor.author","Capece, Vincenzo"],["dc.contributor.author","Garcia Vizcaino, Julio C."],["dc.contributor.author","Schuetz, Anna-Lena"],["dc.contributor.author","Burkhardt, Susanne"],["dc.contributor.author","Benito, Eva"],["dc.contributor.author","Navarro Sala, Magdalena"],["dc.contributor.author","Bahari Javan, Sanaz"],["dc.contributor.author","Haass, Christian"],["dc.contributor.author","Schmid, Bettina"],["dc.contributor.author","Fischer, André"],["dc.contributor.author","Bonn, Stefan"],["dc.date.accessioned","2018-05-30T15:01:05Z"],["dc.date.available","2018-05-30T15:01:05Z"],["dc.date.issued","2016"],["dc.description.abstract","The ability to form memories is a prerequisite for an organism's behavioral adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell types and three time points before and after contextual learning. We found that histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression. Although long-lasting changes were almost exclusive to neurons, learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provide evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring."],["dc.identifier.doi","10.1038/nn.4194"],["dc.identifier.pmid","26656643"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/14808"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1546-1726"],["dc.title","DNA methylation changes in plasticity genes accompany the formation and maintenance of memory"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]