Chronic Presence of Oligomeric A beta Differentially Modulates Spine Parameters in the Hippocampus and Cortex of Mice With Low APP Transgene Expression

DC FieldValueLanguage
dc.contributor.authorHrynchak, Mariya
dc.contributor.authorRierola, Marina
dc.contributor.authorGolovyashkina, Nataliya
dc.contributor.authorPenazzi, Lorene
dc.contributor.authorPump, Wiebke C.
dc.contributor.authorDavid, Bastian
dc.contributor.authorSuendermann, Frederik
dc.contributor.authorBrandt, Roland
dc.contributor.authorBakota, Lidia
dc.date.accessioned2021-12-23T15:56:52Z-
dc.date.available2021-12-23T15:56:52Z-
dc.date.issued2020
dc.identifier.issn16633563
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/2586-
dc.description.abstractAlzheimer's disease is regarded as a synaptopathy with a long presymptomatic phase. Soluble, oligomeric amyloid-beta (A beta) is thought to play a causative role in this disease, which eventually leads to cognitive decline. However, most animal studies have employed mice expressing high levels of the A beta precursor protein (APP) transgene to drive pathology. Here, to understand how the principal neurons in different brain regions cope with moderate, chronically present levels of A beta, we employed transgenic mice expressing equal levels of mouse and human APP carrying a combination of three familial AD (FAD)-linked mutations (Swedish, Dutch, and London), that develop plaques only in old age. We analyzed dendritic spine parameters in hippocampal and cortical brain regions after targeted expression of EGFP to allow high-resolution imaging, followed by algorithm-based evaluation of mice of both sexes from adolescence to old age. We report that A beta species gradually accumulated throughout the life of APP SDL mice, but not the oligomeric forms, and that the amount of membrane-associated oligomers decreased at the onset of plaque formation. We observed an age-dependent loss of thin spines under most conditions as an indicator of a loss of synaptic plasticity in older mice. We further found that hippocampal pyramidal neurons respond to increased A beta levels by lowering spine density and shifting spine morphology, which reached significance in the CA1 subfield. In contrast, the spine density in cortical pyramidal neurons of APP(SDL) mice was unchanged. We also observed an increase in the protein levels of PSD-95 and Arc in the hippocampus and cortex, respectively. Our data demonstrated that increased concentrations of A beta have diverse effects on dendritic spines in the brain and suggest that hippocampal and cortical neurons have different adaptive and compensatory capacity during their lifetime. Our data also indicated that spine morphology differs between sexes in a region-specific manner.
dc.description.sponsorshipDeutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [DFG BR1192/11-2]; Incentive award of the Biology Faculty of the University of Osnabruck; This work was supported by a Deutsche Forschungsgemeinschaft grant to RB (DFG BR1192/11-2) and an Incentive award of the Biology Faculty of the University of Osnabruck for LB.
dc.language.isoen
dc.publisherFRONTIERS RESEARCH FOUNDATION
dc.relation.ispartofFRONTIERS IN SYNAPTIC NEUROSCIENCE
dc.subjectA beta
dc.subjectAlzheimer's disease
dc.subjectALZHEIMERS-DISEASE
dc.subjectAMYLOID-BETA
dc.subjectCOGNITIVE IMPAIRMENT
dc.subjectcortex
dc.subjectdendritic spine
dc.subjectDENDRITIC SPINES
dc.subjectDENTATE GYRUS
dc.subjecthippocampus
dc.subjectLONG-TERM POTENTIATION
dc.subjectNEURONS
dc.subjectNeurosciences
dc.subjectNeurosciences & Neurology
dc.subjectPLASTICITY
dc.subjectSYNAPSE LOSS
dc.subjectTAU-PROTEIN
dc.titleChronic Presence of Oligomeric A beta Differentially Modulates Spine Parameters in the Hippocampus and Cortex of Mice With Low APP Transgene Expression
dc.typejournal article
dc.identifier.doi10.3389/fnsyn.2020.00016
dc.identifier.isiISI:000529428200001
dc.description.volume12
dc.contributor.orcid0000-0003-1152-2093
dc.contributor.orcid0000-0003-0101-1257
dc.publisher.placeEPFL SCIENCE PARK, BLDG D, LAUSANNE, 1015, SWITZERLAND
dcterms.isPartOf.abbreviationFront. Synaptic Neurosci.
dcterms.oaStatusGreen Published, gold
crisitem.author.orcid0000-0003-0101-1257-
crisitem.author.netidBrRo587-
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