Bouter, Yvonne

[["dc.bibliographiccitation.journal","Frontiers in Medicine"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Bouter, Caroline"],["dc.contributor.author","Irwin, Caroline"],["dc.contributor.author","Franke, Timon N."],["dc.contributor.author","Beindorff, Nicola"],["dc.contributor.author","Bouter, Yvonne"],["dc.date.accessioned","2022-01-11T14:06:14Z"],["dc.date.available","2022-01-11T14:06:14Z"],["dc.date.issued","2021"],["dc.description.abstract","Successful back-translating clinical biomarkers and molecular imaging methods of Alzheimer's disease (AD), including positron emission tomography (PET), are very valuable for the evaluation of new therapeutic strategies and increase the quality of preclinical studies. 18 F-Fluorodeoxyglucose (FDG)–PET and 18 F-Florbetaben–PET are clinically established biomarkers capturing two key pathological features of AD. However, the suitability of 18 F-FDG– and amyloid–PET in the widely used 5XFAD mouse model of AD is still unclear. Furthermore, only data on male 5XFAD mice have been published so far, whereas studies in female mice and possible sex differences in 18 F-FDG and 18 F-Florbetaben uptake are missing. The aim of this study was to evaluate the suitability of 18 F-FDG– and 18 F-Florbetaben–PET in 7-month-old female 5XFAD and to assess possible sex differences between male and female 5XFAD mice. We could demonstrate that female 5XFAD mice showed a significant reduction in brain glucose metabolism and increased cerebral amyloid deposition compared with wild type animals, in accordance with the pathology seen in AD patients. Furthermore, we showed for the first time that the hypometabolism in 5XFAD mice is gender-dependent and more pronounced in female mice. Therefore, these results support the feasibility of small animal PET imaging with 18 F-FDG- and 18 F-Florbetaben in 5XFAD mice in both, male and female animals. Moreover, our findings highlight the need to account for sex differences in studies working with 5XFAD mice."],["dc.description.abstract","Successful back-translating clinical biomarkers and molecular imaging methods of Alzheimer's disease (AD), including positron emission tomography (PET), are very valuable for the evaluation of new therapeutic strategies and increase the quality of preclinical studies. 18 F-Fluorodeoxyglucose (FDG)–PET and 18 F-Florbetaben–PET are clinically established biomarkers capturing two key pathological features of AD. However, the suitability of 18 F-FDG– and amyloid–PET in the widely used 5XFAD mouse model of AD is still unclear. Furthermore, only data on male 5XFAD mice have been published so far, whereas studies in female mice and possible sex differences in 18 F-FDG and 18 F-Florbetaben uptake are missing. The aim of this study was to evaluate the suitability of 18 F-FDG– and 18 F-Florbetaben–PET in 7-month-old female 5XFAD and to assess possible sex differences between male and female 5XFAD mice. We could demonstrate that female 5XFAD mice showed a significant reduction in brain glucose metabolism and increased cerebral amyloid deposition compared with wild type animals, in accordance with the pathology seen in AD patients. Furthermore, we showed for the first time that the hypometabolism in 5XFAD mice is gender-dependent and more pronounced in female mice. Therefore, these results support the feasibility of small animal PET imaging with 18 F-FDG- and 18 F-Florbetaben in 5XFAD mice in both, male and female animals. Moreover, our findings highlight the need to account for sex differences in studies working with 5XFAD mice."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3389/fmed.2021.745064"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97859"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation.eissn","2296-858X"],["dc.rights","CC BY 4.0"],["dc.title","Quantitative Brain Positron Emission Tomography in Female 5XFAD Alzheimer Mice: Pathological Features and Sex-Specific Alterations"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","269"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Alzheimer's Disease Reports"],["dc.bibliographiccitation.lastpage","278"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Sichler, Marius E."],["dc.contributor.author","Löw, Maximilian J."],["dc.contributor.author","Schleicher, Eva M."],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Bouter, Yvonne"],["dc.date.accessioned","2021-06-01T10:48:43Z"],["dc.date.available","2021-06-01T10:48:43Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.3233/ADR-190132"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16704"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86031"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","2542-4823"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","Reduced Acoustic Startle Response and Prepulse Inhibition in the Tg4-42 Model of Alzheimer’s Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","94"],["dc.bibliographiccitation.journal","Frontiers in Behavioral Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Schleicher, Eva M."],["dc.contributor.author","Ott, Frederik W."],["dc.contributor.author","Müller, Melanie"],["dc.contributor.author","Silcher, Barbara"],["dc.contributor.author","Sichler, Marius E."],["dc.contributor.author","Löw, Maximilian J."],["dc.contributor.author","Wagner, Jannek M."],["dc.contributor.author","Bouter, Yvonne"],["dc.date.accessioned","2019-07-09T11:51:17Z"],["dc.date.available","2019-07-09T11:51:17Z"],["dc.date.issued","2019"],["dc.description.abstract","The Cannabis plant contains more than 100 currently known phytocannabinoids. Regarding the rising consumption of the non-psychotropic phytocannabinoid cannabidiol (CBD) in people’s everyday life (e.g., beauty products, food and beverages), the importance of studies on the influence of CBD on healthy humans and rodents is evident. Therefore, the behavioral profile of CBD was investigated with a battery of behavioral tests, including motor, anxiety, and memory tests after prolonged CBD treatment. Adult C57Bl/6J wildtype (WT) mice were daily intraperitoneally injected with 20 mg/kg CBD for 6 weeks starting at two different points of ages (3 months and 5 months) to compare the influence of prolonged CBD treatment with a washout period (former group) to the effects of long term CBD treatment (current group). Our results show that CBD treatment does not influence motor performance on an accelerating Rotarod test, while it also results in a lower locomotor activity in the open field (OF). No influence of CBD on spatial learning and long term memory in the Morris Water Maze (MWM) was observed. Memory in the Novel Object Recognition test (NORT) was unaffected by CBD treatment. Two different anxiety tests revealed that CBD does not affect anxiety behavior in the Dark-Light Box (DLB) and OF test. Although, anxiety is altered by current CBD treatment in the Elevated Plus Maze (EPM). Moreover, CBDtreated C57Bl/6J mice showed an unaltered acoustic startle response (ASR) compared to vehicle-treated mice. However, current CBD treatment impairs prepulse inhibition (PPI), a test to analyze sensorimotor gating. Furthermore, prolonged CBD treatment did not affect the hippocampal neuron number. Our results demonstrate that prolonged CBD treatment has no negative effect on the behavior of adult C57Bl/6J mice."],["dc.identifier.doi","10.3389/fnbeh.2019.00094"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16095"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59917"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Prolonged Cannabidiol Treatment Lacks on Detrimental Effects on Memory, Motor Performance and Anxiety in C57BL/6J Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Medicine"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Franke, Timon N."],["dc.contributor.author","Irwin, Caroline"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Brenner, Winfried"],["dc.contributor.author","Beindorff, Nicola"],["dc.contributor.author","Bouter, Caroline"],["dc.contributor.author","Bouter, Yvonne"],["dc.date.accessioned","2021-04-14T08:32:38Z"],["dc.date.available","2021-04-14T08:32:38Z"],["dc.date.issued","2020"],["dc.description.abstract","Imaging biomarkers of Alzheimer's disease (AD) that are able to detect molecular changes in vivo and transgenic animal models mimicking AD pathologies are essential for the evaluation of new therapeutic strategies. Positron-emission tomography (PET) using either 18F-Fluorodeoxyglucose (18F-FDG) or amyloid-tracers is a well-established, non-invasive tool in the clinical diagnostics of AD assessing two major pathological hallmarks. 18F-FDG-PET is able to detect early changes in cerebral glucose metabolism and amyloid-PET shows cerebral amyloid load. However, the suitability of 18F-FDG- and amyloid-PET in the widely used 5XFAD mouse model of AD is unclear as only a few studies on the use of PET biomarkers are available showing some conflicting results. The aim of this study was the evaluation of 18F-FDG-PET and amyloid-PET in 5XFAD mice in comparison to neurological deficits and neuropathological changes. Seven- and 12-month-old male 5XFAD mice showed a significant reduction in brain glucose metabolism in 18F-FDG-PET and amyloid-PET with 18F-Florbetaben demonstrated an increased cerebral amyloid deposition (n = 4–6 per group). Deficits in spatial reference memory were detected in 12-month-old 5XFAD mice in the Morris Water Maze (n = 10–12 per group). Furthermore, an increased plaque load and gliosis could be proven immunohistochemically in 5XFAD mice (n = 4–6 per group). PET biomarkers 18F-FDG and 18F-Florbetaben detected cerebral hypometabolism and increased plaque load even before the onset of severe memory deficits. Therefore, the 5XFAD mouse model of AD is well-suited for in vivo monitoring of AD pathologies and longitudinal testing of new therapeutic approaches."],["dc.identifier.doi","10.3389/fmed.2020.00529"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17550"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83972"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","2296-858X"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","In vivo Imaging With 18F-FDG- and 18F-Florbetaben-PET/MRI Detects Pathological Changes in the Brain of the Commonly Used 5XFAD Mouse Model of Alzheimer's Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Medicine"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Bouter, Caroline"],["dc.contributor.author","Bouter, Yvonne"],["dc.date.accessioned","2020-12-10T18:44:26Z"],["dc.date.available","2020-12-10T18:44:26Z"],["dc.date.issued","2019"],["dc.description.abstract","Suitable animal models and in vivo biomarkers are essential for development and evaluation of new therapeutic strategies in Alzheimer's disease (AD). 18F-Fluorodeoxyglucose (18F-FDG)-positron-emission tomography (PET) is an imaging biomarker that allows the assessment of cerebral glucose metabolism in vivo. While 18F-FDG-PET/CT is an established tool in the evaluation of AD patients, its role in preclinical studies with AD mouse models remains unclear. Here, we want to review available studies on 18F-FDG-PET/CT in AD mouse models in order to evaluate the method and its impact in preclinical AD research. Only a limited number of studies using 18F-FDG-PET in AD mice were carried out so far showing contradictory findings in cerebral FDG uptake. Methodological differences as well as underlying pathological features of used mouse models seem to be accountable for those varying results. However, 18F-FDG-PET can be a valuable tool in longitudinal in vivo therapy monitoring with a lot of potential for future studies."],["dc.identifier.doi","10.3389/fmed.2019.00071"],["dc.identifier.eissn","2296-858X"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17582"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78450"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","2296-858X"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","18F-FDG-PET in Mouse Models of Alzheimer's Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","107"],["dc.bibliographiccitation.journal","Frontiers in Behavioral Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Wagner, Jannek M."],["dc.contributor.author","Sichler, Marius E."],["dc.contributor.author","Schleicher, Eva M."],["dc.contributor.author","Franke, Timon N."],["dc.contributor.author","Irwin, Caroline"],["dc.contributor.author","Löw, Maximilian Johannes"],["dc.contributor.author","Beindorff, Nicola"],["dc.contributor.author","Bouter, Caroline"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Bouter, Yvonne"],["dc.date.accessioned","2019-07-09T11:51:44Z"],["dc.date.available","2019-07-09T11:51:44Z"],["dc.date.issued","2019"],["dc.description.abstract","Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia. Hallmarks of AD are memory impairments and cognitive deficits, but non-cognitive impairments, especially motor dysfunctions are also associated with the disease and may even precede classic clinical symptoms. With an aging society and increasing hospitalization of the elderly, motor deficits are of major interest to improve independent activities in daily living. Consistent with clinical findings, a variety of AD mouse models develop motor deficits as well. We investigated the motor function of 3- and 7-month-old Tg4-42 mice in comparison to wild-type controls and 5XFAD mice and discuss the results in context with several other AD mouse model. Our study shows impaired balance and motor coordination in aged Tg4-42 mice in the balance beam and rotarod test, while general locomotor activity and muscle strength is not impaired at 7 months. The cerebellum is a major player in the regulation and coordination of balance and locomotion through practice. Particularly, the rotarod test is able to detect cerebellar deficits. Furthermore, supposed cerebellar impairment was verified by 18F-FDG PET/MRI. Aged Tg4-42 mice showed reduced cerebellar glucose metabolism in the 18F-FDG PET. Suggesting that, deficits in coordination and balance are most likely due to cerebellar impairment. In conclusion, Tg4-42 mice develop motor deficits before memory deficits, without confounding memory test. Thus, making the Tg4-42 mouse model a good model to study the effects on cognitive decline of therapies targeting motor impairments."],["dc.identifier.doi","10.3389/fnbeh.2019.00107"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16180"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59999"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Analysis of Motor Function in the Tg4-42 Mouse Model of Alzheimer’s Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Neuroscience"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Bouter, Yvonne"],["dc.contributor.author","Kacprowski, Tim"],["dc.contributor.author","Rößler, Fanny"],["dc.contributor.author","Jensen, Lars R."],["dc.contributor.author","Kuss, Andreas W."],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2021-04-14T08:32:38Z"],["dc.date.available","2021-04-14T08:32:38Z"],["dc.date.issued","2020"],["dc.description.abstract","The transcriptome of non-coding RNA (ncRNA) species is increasingly focused in Alzheimer’s disease (AD) research. NcRNAs comprise, among others, transfer RNAs, long non-coding RNAs and microRNAs (miRs), each with their own specific biological function. We used smallRNASeq to assess miR expression in the hippocampus of young (3 month old) and aged (8 month old) Tg4-42 mice, a model system for sporadic AD, as well as age-matched wildtype controls. Tg4-42 mice express N-truncated Aβ4–42, develop age-related neuron loss, reduced neurogenesis and behavioral deficits. Our results do not only confirm known miR-AD associations in Tg4-42 mice, but more importantly pinpoint 22 additional miRs associated to the disease. Twenty-five miRs were differentially expressed in both aged Tg4-42 and aged wildtype mice while eight miRs were differentially expressed only in aged wildtype mice, and 33 only in aged Tg4-42 mice. No significant alteration in the miRNome was detected in young mice, which indicates that the changes observed in aged mice are down-stream effects of Aβ-induced pathology in the Tg4-42 mouse model for AD. Targets of those miRs were predicted using miRWalk. For miRs that were differentially expressed only in the Tg4-42 model, 128 targets could be identified, whereas 18 genes were targeted by miRs only differentially expressed in wildtype mice and 85 genes were targeted by miRs differentially expressed in both mouse models. Genes targeted by differentially expressed miRs in the Tg4-42 model were enriched for negative regulation of long-term synaptic potentiation, learning or memory, regulation of trans-synaptic signaling and modulation of chemical synaptic transmission obtained. This untargeted miR sequencing approach supports previous reports on the Tg4-42 mice as a valuable model for AD. Furthermore, it revealed miRs involved in AD, which can serve as biomarkers or therapeutic targets."],["dc.identifier.doi","10.3389/fnins.2020.580524"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83970"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1662-453X"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","miRNA Alterations Elicit Pathways Involved in Memory Decline and Synaptic Function in the Hippocampus of Aged Tg4-42 Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","56"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communications"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Antonios, Gregory"],["dc.contributor.author","Saiepour, Nasrin"],["dc.contributor.author","Bouter, Yvonne"],["dc.contributor.author","Richard, Bernhard C."],["dc.contributor.author","Paetau, Anders"],["dc.contributor.author","Verkkoniemi-Ahola, Auli"],["dc.contributor.author","Lannfelt, Lars"],["dc.contributor.author","Ingelsson, Martin"],["dc.contributor.author","Kovacs, Gabor G."],["dc.contributor.author","Pillot, Thierry"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2019-07-09T11:41:53Z"],["dc.date.available","2019-07-09T11:41:53Z"],["dc.date.issued","2013"],["dc.description.abstract","Abstract Background The amyloid hypothesis in Alzheimer disease (AD) considers amyloid β peptide (Aβ) deposition causative in triggering down-stream events like neurofibrillary tangles, cell loss, vascular damage and memory decline. In the past years N-truncated Aβ peptides especially N-truncated pyroglutamate AβpE3-42 have been extensively studied. Together with full-length Aβ1–42 and Aβ1–40, N-truncated AβpE3-42 and Aβ4–42 are major variants in AD brain. Although Aβ4–42 has been known for a much longer time, there is a lack of studies addressing the question whether AβpE3-42 or Aβ4–42 may precede the other in Alzheimer’s disease pathology. Results Using different Aβ antibodies specific for the different N-termini of N-truncated Aβ, we discovered that Aβ4-x preceded AβpE3-x intraneuronal accumulation in a transgenic mouse model for AD prior to plaque formation. The novel Aβ4-x immunoreactive antibody NT4X-167 detected high molecular weight aggregates derived from N-truncated Aβ species. While NT4X-167 significantly rescued Aβ4–42 toxicity in vitro no beneficial effect was observed against Aβ1–42 or AβpE3-42 toxicity. Phenylalanine at position four of Aβ was imperative for antibody binding, because its replacement with alanine or proline completely prevented binding. Although amyloid plaques were observed using NT4X-167 in 5XFAD transgenic mice, it barely reacted with plaques in the brain of sporadic AD patients and familial cases with the Arctic, Swedish and the presenilin-1 PS1Δ9 mutation. A consistent staining was observed in blood vessels in all AD cases with cerebral amyloid angiopathy. There was no cross-reactivity with other aggregates typical for other common neurodegenerative diseases showing that NT4X-167 staining is specific for AD. Conclusions Aβ4-x precedes AβpE3-x in the well accepted 5XFAD AD mouse model underlining the significance of N-truncated species in AD pathology. NT4X-167 therefore is the first antibody reacting with Aβ4-x and represents a novel tool in Alzheimer research."],["dc.identifier.doi","10.1186/2051-5960-1-56"],["dc.identifier.pmid","24252153"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12500"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58537"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","N-truncated Abeta starting with position four: early intraneuronal accumulation and rescue of toxicity using NT4X-167, a novel monoclonal antibody"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","5451"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Curdt, Nadine"],["dc.contributor.author","Schmitt, Franziska W."],["dc.contributor.author","Bouter, Caroline"],["dc.contributor.author","Iseni, Trendelina"],["dc.contributor.author","Weile, Hanna C."],["dc.contributor.author","Altunok, Berfin"],["dc.contributor.author","Beindorff, Nicola"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Cooke, Matthew B."],["dc.contributor.author","Bouter, Yvonne"],["dc.date.accessioned","2022-05-02T08:02:10Z"],["dc.date.available","2022-05-02T08:02:10Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract Spatial disorientation is one of the earliest symptoms in Alzheimer’s disease and allocentric deficits can already be detected in the asymptomatic preclinical stages of the disease. The Morris Water Maze (MWM) is used to study spatial learning in rodent models. Here we investigated the spatial memory of female 3, 7 and 12 month-old Alzheimer Tg4-42 mice in comparison to wild-type control animals. Conventional behavior analysis of escape latencies and quadrant preference revealed spatial memory and reference memory deficits in female 7 and 12 month-old Tg4-42 mice. In contrast, conventional analysis of the MWM indicated an intact spatial memory in 3 month-old Tg4-42 mice. However, a detailed analysis of the swimming strategies demonstrated allocentric-specific memory deficits in 3 month-old Tg4-42 mice before the onset of severe memory deficits. Furthermore, we could show that the spatial reference memory deficits in aged Tg4-42 animals are caused by the lack of allocentric and spatial strategies. Analyzing search strategies in the MWM allows to differentiate between hippocampus-dependent allocentric and hippocampus-independent egocentric search strategies. The spatial navigation impairments in young Tg4-42 mice are well in line with the hypometabolism and synaptic deficits in the hippocampus. Therefore, analyzing search strategies in the Tg4-42 model can be a powerful tool for preclinical drug testing and identifying early therapeutic successes."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1038/s41598-022-09270-1"],["dc.identifier.pii","9270"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107247"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-561"],["dc.relation.eissn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Search strategy analysis of Tg4-42 Alzheimer Mice in the Morris Water Maze reveals early spatial navigation deficits"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","123"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","136"],["dc.bibliographiccitation.volume","126"],["dc.contributor.author","Storck, Steffen E."],["dc.contributor.author","Meister, Sabrina"],["dc.contributor.author","Nahrath, Julius"],["dc.contributor.author","Meissner, Julius N."],["dc.contributor.author","Schubert, Nils"],["dc.contributor.author","Di Spiezio, Alessandro"],["dc.contributor.author","Baches, Sandra"],["dc.contributor.author","Vandenbroucke, Roosmarijn E."],["dc.contributor.author","Bouter, Yvonne"],["dc.contributor.author","Prikulis, Ingrid"],["dc.contributor.author","Korth, Carsten"],["dc.contributor.author","Weggen, Sascha"],["dc.contributor.author","Heimann, Axel"],["dc.contributor.author","Schwaninger, Markus"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Pietrzik, Claus U."],["dc.date.accessioned","2018-11-07T10:21:33Z"],["dc.date.available","2018-11-07T10:21:33Z"],["dc.date.issued","2016"],["dc.description.abstract","According to the neurovascular hypothesis, impairment of low-density lipoprotein receptor-related protein-1 (LRP1) in brain capillaries of the blood-brain barrier (BBB) contributes to neurotoxic amyloid-beta (A beta) brain accumulation and drives Alzheimer's disease (AD) pathology. However, due to conflicting reports on the involvement of LRP1 in A beta transport and the expression of LRP1 in brain endothelium, the role of LRP1 at the BBB is uncertain. As global Lrp1 deletion in mice is lethal, appropriate models to study the function of LRP1 are lacking. Moreover, the relevance of systemic A beta clearance to AD pathology remains unclear, as no BBB-specific knockout models have been available. Here, we developed transgenic mouse strains that allow for tamoxifen-inducible deletion of Lrp1 specifically within brain endothelial cells (Slo1c1-CreER(Tz) Lrp1(fl/fl) mice) and used these mice to accurately evaluate LRP1-mediated A beta BBB clearance in vivo. Selective deletion of Lrp1 in the brain endothelium of C57BL/6 mice strongly reduced brain efflux of injected [I-125] A beta(1-42). Additionally, in the 5xFAD mouse model of AD, brain endothelial-specific Lrp1 deletion reduced plasma A beta levels and elevated soluble brain A beta, leading to aggravated spatial learning and memory deficits, thus emphasizing the importance of systemic AD elimination via the BBB. Together, our results suggest that receptor-mediated A beta BBB clearance may be a potential target for treatment and prevention of A beta brain accumulation in AD."],["dc.identifier.doi","10.1172/JCI81108"],["dc.identifier.isi","000367765600015"],["dc.identifier.pmid","26619118"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13318"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42117"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Clinical Investigation Inc"],["dc.relation.issn","1558-8238"],["dc.relation.issn","0021-9738"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Endothelial LRP1 transports amyloid-beta(1-42) across the blood-brain barrier"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]