Saul, Anika

[["dc.bibliographiccitation.firstpage","319"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.bibliographiccitation.lastpage","327"],["dc.bibliographiccitation.volume","54"],["dc.contributor.author","Saul, Anika"],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2020-12-10T14:14:23Z"],["dc.date.available","2020-12-10T14:14:23Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1007/s12035-015-9674-4"],["dc.identifier.eissn","1559-1182"],["dc.identifier.issn","0893-7648"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71339"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Endogenous Apolipoprotein E (ApoE) Fragmentation Is Linked to Amyloid Pathology in Transgenic Mouse Models of Alzheimer’s Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1416"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.lastpage","1425"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Saul, Anika"],["dc.contributor.author","Lashley, Tammaryn"],["dc.contributor.author","Revesz, Tamas"],["dc.contributor.author","Holton, Janice"],["dc.contributor.author","Ghiso, Jorge A."],["dc.contributor.author","Coomaraswamy, Janaky"],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2018-11-07T09:25:51Z"],["dc.date.available","2018-11-07T09:25:51Z"],["dc.date.issued","2013"],["dc.description.abstract","Familial British and familial Danish dementia (FDD) are progressive neurodegenerative disorders characterized by cerebral deposition of the amyloidogenic peptides ABri and ADan, respectively. These amyloid peptides start with an N-terminal glutamate residue, which can be posttranslationally converted into a pyroglutamate (pGlu) modified form, a mechanism which has been extensively described to be relevant for amyloid-beta (A beta) peptides in Alzheimer's disease. Like pGlu-A beta peptides, pGlu-ABri peptides have an increased aggregation propensity and show higher toxicity on human neuroblastoma cells as their nonmodified counterparts. We have generated novel N-terminal specific antibodies detecting the pGlu-modified forms of ABri and ADan peptides. With these antibodies we were able to identify abundant extracellular amyloid plaques, vascular, and parenchymal deposits in human familial British dementia and FDD brain tissue, and in a mouse model for FDD. Double-stainings using C-terminal specific antibodies in human samples revealed that highly aggregated pGlu-ABri and pGlu-ADan peptides are mainly present in plaque cores and central vascular deposits, leading to the assumption that these peptides have seeding properties. Furthermore, in an FDD-mouse model ADan peptides were detected in presynaptic terminals of the hippocampus where they might contribute to impaired synaptic transmission. These similarities of ABri and ADan to A beta in Alzheimer's disease suggest that the post-translational pGlu-modification of amyloid peptides might represent a general pathological mechanism leading to increased aggregation and toxicity in these forms of degenerative dementias. (C) 2013 Elsevier Inc. All rights reserved."],["dc.description.sponsorship","Fritz-Thyssen-Foundation; NIH [R01 AG030539]"],["dc.identifier.doi","10.1016/j.neurobiolaging.2012.11.014"],["dc.identifier.isi","000315729500010"],["dc.identifier.pmid","23261769"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30156"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0197-4580"],["dc.title","Abundant pyroglutamate-modified ABri and ADan peptides in extracellular and vascular amyloid deposits in familial British and Danish dementias"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2564"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.lastpage","2573"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Saul, Anika"],["dc.contributor.author","Sprenger, Frederik"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2021-06-01T10:49:48Z"],["dc.date.available","2021-06-01T10:49:48Z"],["dc.date.issued","2013"],["dc.identifier.doi","10.1016/j.neurobiolaging.2013.05.003"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86421"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","0197-4580"],["dc.title","Accelerated tau pathology with synaptic and neuronal loss in a novel triple transgenic mouse model of Alzheimer's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","106"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neuropathology and Applied Neurobiology"],["dc.bibliographiccitation.lastpage","120"],["dc.bibliographiccitation.volume","40"],["dc.contributor.author","Haertig, Wolfgang"],["dc.contributor.author","Saul, Anika"],["dc.contributor.author","Kacza, Johannes"],["dc.contributor.author","Grosche, Jens"],["dc.contributor.author","Goldhammer, Simone"],["dc.contributor.author","Michalski, D."],["dc.contributor.author","Wirths, Oliver"],["dc.date.accessioned","2018-11-07T09:44:30Z"],["dc.date.available","2018-11-07T09:44:30Z"],["dc.date.issued","2014"],["dc.description.abstract","AimsCurrently available animal models incompletely capture the complex pathophysiology of Alzheimer's disease (AD), typically involving -amyloidosis, neurofibrillary tangle formation and loss of basal forebrain cholinergic projection neurones (CPN). While age-dependent -amyloidosis and tau hyperphosphorylation are mimicked in triple-transgenic mice (3xTg), experimental induction of CPN loss in these mice is still lacking. Here, we introduce a more-complex animal model of AD by inducing cellular loss of CPN in an already existing transgenic background aiming to elucidate subsequent changes of hippocampal -amyloid (A) and tau pathology. MethodsTwelve-month-old 3xTg mice intracerebroventricularly received the rabbit-anti-low affinity neurotrophin receptor p75-saporin, an immunotoxin specifically targeting forebrain CPN. After histochemical verification of immunolesion in immersion-fixed forebrains, markers of A and tau metabolism were analysed using quantitative Western blot analyses of hippocampi from these mice. In parallel, these markers and glial activation were investigated by multiple immunofluorescence labelling of perfusion-fixed hippocampi and confocal laser-scanning microscopy. ResultsFour months after immunolesion, the selective lesion of CPN was verified by disappearance of choline acetyltransferase and p75 immunolabelling. Biochemical analysis of hippocampi from immunolesioned mice revealed enhanced levels of A, amyloid precursor protein (APP) and its fragment C99. Furthermore, immunolesion-induced increase in levels of phospho-tau and tau with AD-like conformation were seen in 16-month-old mice. Immunofluorescence staining confirmed an age-dependent occurrence of hippocampal A-deposits and phospho-tau, and demonstrated drastic gliosis around A-plaques after immunolesion. ConclusionOverall, this extended model promises further insights into the complexity of AD and contributes to novel treatment strategies also targeting the cholinergic system."],["dc.description.sponsorship","Alzheimer Forschung Initiative e.V."],["dc.identifier.doi","10.1111/nan.12050"],["dc.identifier.isi","000331059100003"],["dc.identifier.pmid","23566195"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34410"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1365-2990"],["dc.relation.issn","0305-1846"],["dc.title","Immunolesion-induced loss of cholinergic projection neurones promotes beta-amyloidosis and tau hyperphosphorylation in the hippocampus of triple-transgenic mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Kaczmarek-Hajek, Karina"],["dc.contributor.author","Zhang, Jiong"],["dc.contributor.author","Kopp, Robin"],["dc.contributor.author","Grosche, Antje"],["dc.contributor.author","Rissiek, Björn"],["dc.contributor.author","Saul, Anika"],["dc.contributor.author","Bruzzone, Santina"],["dc.contributor.author","Engel, Tobias"],["dc.contributor.author","Jooss, Tina"],["dc.contributor.author","Krautloher, Anna"],["dc.contributor.author","Nicke, Annette"],["dc.date.accessioned","2022-03-01T11:44:33Z"],["dc.date.available","2022-03-01T11:44:33Z"],["dc.date.issued","2018"],["dc.description.abstract","The P2X7 channel is involved in the pathogenesis of various CNS diseases. An increasing number of studies suggest its presence in neurons where its putative functions remain controversial for more than a decade. To resolve this issue and to provide a model for analysis of P2X7 functions, we generated P2X7 BAC transgenic mice that allow visualization of functional EGFP-tagged P2X7 receptors in vivo. Extensive characterization of these mice revealed dominant P2X7-EGFP protein expression in microglia, Bergmann glia, and oligodendrocytes, but not in neurons. These findings were further validated by microglia- and oligodendrocyte-specific P2X7 deletion and a novel P2X7-specific nanobody. In addition to the first quantitative analysis of P2X7 protein expression in the CNS, we show potential consequences of its overexpression in ischemic retina and post-traumatic cerebral cortex grey matter. This novel mouse model overcomes previous limitations in P2X7 research and will help to determine its physiological roles and contribution to diseases."],["dc.description.abstract","The human body relies on a molecule called ATP as an energy source and as a messenger. When cells die, for example if they are damaged or because of inflammation, they release large amounts of ATP into their environment. Their neighbors can detect the outpouring of ATP through specific receptors, the proteins that sit at the cell’s surface and can bind external agents. Scientists believe that one of these ATP-binding receptors, P2X7, responds to high levels of ATP by triggering a cascade of reactions that results in inflammation and cell death. P2X7 also seems to play a role in several brain diseases such as epilepsia and Alzheimer’s, but the exact mechanisms are not known. In particular, how this receptor is involved in the death of neurons is unclear, and researchers still debate whether P2X7 is present in neurons and in other types of brain cells. To answer this, Kaczmarek-Hájek, Zhang, Kopp et al. created genetically modified mice in which the P2X7 receptors carry a fluorescent dye. Powerful microscopes can pick up the light signal from the dye and help to reveal which cells have the receptors. These experiments show that neurons do not carry the protein; instead, P2X7 is present in certain brain cells that keep the neurons healthy. For example, it is found in the immune cells that ‘clean up’ the organ, and the cells that support and insulate neurons. Kaczmarek-Hájek et al. further provide preliminary data suggesting that, under certain conditions, if too many P2X7 receptors are present in these cells neuronal damage might be increased. It is therefore possible that the brain cells that carry P2X7 indirectly contribute to the death of neurons when large amounts of ATP are released. The genetically engineered mouse designed for the experiments could be used in further studies to dissect the role that P2X7 plays in diseases of the nervous system. In particular, this mouse model might help to understand whether the receptor could become a drug target for neurodegenerative conditions."],["dc.description.abstract","The P2X7 channel is involved in the pathogenesis of various CNS diseases. An increasing number of studies suggest its presence in neurons where its putative functions remain controversial for more than a decade. To resolve this issue and to provide a model for analysis of P2X7 functions, we generated P2X7 BAC transgenic mice that allow visualization of functional EGFP-tagged P2X7 receptors in vivo. Extensive characterization of these mice revealed dominant P2X7-EGFP protein expression in microglia, Bergmann glia, and oligodendrocytes, but not in neurons. These findings were further validated by microglia- and oligodendrocyte-specific P2X7 deletion and a novel P2X7-specific nanobody. In addition to the first quantitative analysis of P2X7 protein expression in the CNS, we show potential consequences of its overexpression in ischemic retina and post-traumatic cerebral cortex grey matter. This novel mouse model overcomes previous limitations in P2X7 research and will help to determine its physiological roles and contribution to diseases."],["dc.description.abstract","The human body relies on a molecule called ATP as an energy source and as a messenger. When cells die, for example if they are damaged or because of inflammation, they release large amounts of ATP into their environment. Their neighbors can detect the outpouring of ATP through specific receptors, the proteins that sit at the cell’s surface and can bind external agents. Scientists believe that one of these ATP-binding receptors, P2X7, responds to high levels of ATP by triggering a cascade of reactions that results in inflammation and cell death. P2X7 also seems to play a role in several brain diseases such as epilepsia and Alzheimer’s, but the exact mechanisms are not known. In particular, how this receptor is involved in the death of neurons is unclear, and researchers still debate whether P2X7 is present in neurons and in other types of brain cells. To answer this, Kaczmarek-Hájek, Zhang, Kopp et al. created genetically modified mice in which the P2X7 receptors carry a fluorescent dye. Powerful microscopes can pick up the light signal from the dye and help to reveal which cells have the receptors. These experiments show that neurons do not carry the protein; instead, P2X7 is present in certain brain cells that keep the neurons healthy. For example, it is found in the immune cells that ‘clean up’ the organ, and the cells that support and insulate neurons. Kaczmarek-Hájek et al. further provide preliminary data suggesting that, under certain conditions, if too many P2X7 receptors are present in these cells neuronal damage might be increased. It is therefore possible that the brain cells that carry P2X7 indirectly contribute to the death of neurons when large amounts of ATP are released. The genetically engineered mouse designed for the experiments could be used in further studies to dissect the role that P2X7 plays in diseases of the nervous system. In particular, this mouse model might help to understand whether the receptor could become a drug target for neurodegenerative conditions."],["dc.identifier.doi","10.7554/eLife.36217"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103049"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","2050-084X"],["dc.title","Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]