DC Element | Wert | Sprache |
dc.contributor.author | Shahani, Neelam | |
dc.contributor.author | Subramaniam, Srinivasa | |
dc.contributor.author | Wolf, Tobias | |
dc.contributor.author | Tackenberg, Christian | |
dc.contributor.author | Brandt, Roland | |
dc.date.accessioned | 2021-12-23T16:09:39Z | - |
dc.date.available | 2021-12-23T16:09:39Z | - |
dc.date.issued | 2006 | |
dc.identifier.issn | 02706474 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/8916 | - |
dc.description.abstract | Alzheimer's disease ( AD) is characterized by progressive loss of neurons in selected brain regions, extracellular accumulations of amyloid beta, and intracellular fibrils containing hyperphosphorylated tau. Tau mutations in familial tauopathies confirmed a central role of tau pathology; however, the role of tau alteration and the sequence of tau-dependent neurodegeneration in AD remain elusive. Using Sindbis virus-mediated expression of AD-relevant tau constructs in hippocampal slices, we show that disease-like tau modifications affect tau phosphorylation at selected sites, induce Alz50/MC1-reactive pathological tau conformation, cause accumulation of insoluble tau, and induce region-specific neurodegeneration. Live imaging demonstrates that tau-dependent degeneration is associated with the development of a ``ballooned'' phenotype, a distinct feature of cell death. Spine density and morphology is not altered as judged from algorithm-based evaluation of dendritic spines, suggesting that synaptic integrity is remarkably stable against tau-dependent degeneration. The data provide evidence that tau-induced cell death involves apoptotic as well as nonapoptotic mechanisms. Furthermore, they demonstrate that targeted expression of tau in hippocampal slices provides a novel model to analyze tau modification and spatiotemporal dynamics of tau-dependent neurodegeneration in an authentic CNS environment. | |
dc.language.iso | en | |
dc.publisher | SOC NEUROSCIENCE | |
dc.relation.ispartof | JOURNAL OF NEUROSCIENCE | |
dc.subject | ACTIVATED PROTEIN-KINASE | |
dc.subject | BALLOONED NEURONS | |
dc.subject | BRAIN | |
dc.subject | CELL-DEATH | |
dc.subject | DENDRITIC SPINES | |
dc.subject | DNA FRAGMENTATION | |
dc.subject | hippocampus | |
dc.subject | MICE | |
dc.subject | neurodegeneration | |
dc.subject | NEUROFIBRILLARY TANGLES | |
dc.subject | Neurosciences | |
dc.subject | Neurosciences & Neurology | |
dc.subject | PAIRED HELICAL FILAMENTS | |
dc.subject | PHOSPHORYLATION | |
dc.subject | sindbis virus | |
dc.subject | spines | |
dc.subject | tauopathy | |
dc.title | Tau aggregation and progressive neuronal degeneration in the absence of changes in spine density and morphology after targeted expression of Alzheimer's disease-relevant tau constructs in organotypic hippocampal slices | |
dc.type | journal article | |
dc.identifier.doi | 10.1523/JNEUROSCI.4245-05.2006 | |
dc.identifier.isi | ISI:000238040400030 | |
dc.description.volume | 26 | |
dc.description.issue | 22 | |
dc.description.startpage | 6103 | |
dc.description.endpage | 6114 | |
dc.contributor.orcid | 0000-0003-0101-1257 | |
dc.contributor.orcid | 0000-0002-0019-3055 | |
dc.publisher.place | 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA | |
dcterms.isPartOf.abbreviation | J. Neurosci. | |
dcterms.oaStatus | Green Accepted, Bronze, Green Published | |
crisitem.author.orcid | 0000-0003-0101-1257 | - |
crisitem.author.netid | BrRo587 | - |