Koehler, Christoph, Dinekov, Maja and Goetz, Juergen (2014). Granulovacuolar degeneration and unfolded protein response in mouse models of tauopathy and A beta amyloidosis. Neurobiol. Dis., 71. S. 169 - 180. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1095-953X
Full text not available from this repository.Abstract
Histopathological studies on the brains of tauopathy cases including cases with Alzheimer's disease (AD) demonstrate that neurons with hyperphosphorylated protein tau display granulovacuolar degeneration (GVD), as evidenced by vacuolar lesions harboring a central granule, together with markers of the activated unfolded protein response (UPR). In order to examine whether this hallmark is reproduced in animal models we studied the presence of GVD and the activated UPR in two complementary mouse models, pR5 mice with a tau pathology and APPSLxPS1mut mice with an amyloid plaque pathology. Neither GVD nor a significant activation of the UPR was found in both APPSLxPS1mut mice and in those regions in the pR5 brain where only neurons with an early stage of tau hyperphosphorylation were present In contrast, those neurons that displayed a tau phospho-epitope signature that only appeared in old pR5 mice and also correlated with Gallyas-positive tangle staining harbored granulovacuolar lesions that were labeled with the GVD markers casein kinases 1 delta and 1 epsilon. Granulovacuolar lesions in pR5 mice were also labeled with the UPR markers phosphorylated PKR-like endoplasmic reticulum kinase, phosphorylated inositol-requiring enzyme 1 alpha and phosphorylated eukaryotic initiation factor 2 alpha. However, GVD was rarely observed in neurons bearing mature neurofibrillary tangles as evidenced by Congo red staining. Our results suggest that NFT-formation activates the UPR in pR5 mice and that it is the early stages of neurofibrillary tangle formation that are accompanied by GVD, in line with observations from studies on human autopsy cases. (C) 2014 Elsevier Inc. All rights reserved.
Item Type: | Journal Article | ||||||||||||||||
Creators: |
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URN: | urn:nbn:de:hbz:38-425392 | ||||||||||||||||
DOI: | 10.1016/j.nbd.2014.07.006 | ||||||||||||||||
Journal or Publication Title: | Neurobiol. Dis. | ||||||||||||||||
Volume: | 71 | ||||||||||||||||
Page Range: | S. 169 - 180 | ||||||||||||||||
Date: | 2014 | ||||||||||||||||
Publisher: | ACADEMIC PRESS INC ELSEVIER SCIENCE | ||||||||||||||||
Place of Publication: | SAN DIEGO | ||||||||||||||||
ISSN: | 1095-953X | ||||||||||||||||
Language: | English | ||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||
Subjects: | no entry | ||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/42539 |
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