Transduced Wild-Type but Not P301S Mutated Human Tau Shows Hyperphosphorylation in Transgenic Mice Overexpressing A30P Mutated Human Alpha-Synuclein
(2013) In Neurodegenerative Diseases 12(2). p.91-102- Abstract
- Neuropathological and cell culture studies suggest that tau and alpha-synuclein pathologies may promote each other. To study the relevance and functional implications of these findings in vivo, we transduced hippocampal neurons of wild-type or human A30P alpha-synuclein transgenic mice with wild-type or P301S mutated human tau using an adeno-associated virus vector. Green fluorescent protein transduction was used as a control. We assessed spontaneous exploratory activity, anxiety and spatial learning and memory 11 weeks after the transduction and perfused the mice for histology. The transduced tau was mainly found in axon terminals and largely restricted within the hippocampi. In addition, neurons around the injection site showed... (More)
- Neuropathological and cell culture studies suggest that tau and alpha-synuclein pathologies may promote each other. To study the relevance and functional implications of these findings in vivo, we transduced hippocampal neurons of wild-type or human A30P alpha-synuclein transgenic mice with wild-type or P301S mutated human tau using an adeno-associated virus vector. Green fluorescent protein transduction was used as a control. We assessed spontaneous exploratory activity, anxiety and spatial learning and memory 11 weeks after the transduction and perfused the mice for histology. The transduced tau was mainly found in axon terminals and largely restricted within the hippocampi. In addition, neurons around the injection site showed cytoplasmic staining for human tau in both wild-type and A30P mice. Of these tau-positive neurons, 44% in A30P mice but only 3% in wild-type mice receiving human wild-type tau transduction formed paired helical filament-1 (PHF-1)-positive cytoplasmic densities. In contrast, only 1% of tau-positive neurons were also PHF-1 positive after transduction with P301S tau in mice of either genotype. Transduction of P301S tau reduced swimming speed but otherwise tau transduction had no significant behavioral consequences. Cytoplasmic PHF-1 densities were associated with poor spatial memory in wild-type mice but slightly improved memory in A30P mice, indicating that also tau hyperphosphorylation does not necessarily compromise neural functions. These data demonstrate that alpha-synuclein promotes tau hyperphosphorylation depending on the amino acids on the 301 site. Copyright (C) 2012 S. Karger AG, Basel (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4050266
- author
- Oksman, M. ; Wisman, Liselijn LU ; Jiang, H. ; Miettinen, P. ; Kirik, Deniz LU and Tanila, H.
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Parkinson's disease, Lewy body dementia, Neurofibrillary tangles, Hippocampus, Memory
- in
- Neurodegenerative Diseases
- volume
- 12
- issue
- 2
- pages
- 91 - 102
- publisher
- Karger
- external identifiers
-
- wos:000322557800004
- scopus:84881148136
- pmid:22948283
- ISSN
- 1660-2862
- DOI
- 10.1159/000341596
- language
- English
- LU publication?
- yes
- id
- 193c03a4-cae4-4aa8-8c5d-1f79ef56f41b (old id 4050266)
- date added to LUP
- 2016-04-01 10:01:01
- date last changed
- 2022-05-17 19:01:16
@article{193c03a4-cae4-4aa8-8c5d-1f79ef56f41b,
abstract = {{Neuropathological and cell culture studies suggest that tau and alpha-synuclein pathologies may promote each other. To study the relevance and functional implications of these findings in vivo, we transduced hippocampal neurons of wild-type or human A30P alpha-synuclein transgenic mice with wild-type or P301S mutated human tau using an adeno-associated virus vector. Green fluorescent protein transduction was used as a control. We assessed spontaneous exploratory activity, anxiety and spatial learning and memory 11 weeks after the transduction and perfused the mice for histology. The transduced tau was mainly found in axon terminals and largely restricted within the hippocampi. In addition, neurons around the injection site showed cytoplasmic staining for human tau in both wild-type and A30P mice. Of these tau-positive neurons, 44% in A30P mice but only 3% in wild-type mice receiving human wild-type tau transduction formed paired helical filament-1 (PHF-1)-positive cytoplasmic densities. In contrast, only 1% of tau-positive neurons were also PHF-1 positive after transduction with P301S tau in mice of either genotype. Transduction of P301S tau reduced swimming speed but otherwise tau transduction had no significant behavioral consequences. Cytoplasmic PHF-1 densities were associated with poor spatial memory in wild-type mice but slightly improved memory in A30P mice, indicating that also tau hyperphosphorylation does not necessarily compromise neural functions. These data demonstrate that alpha-synuclein promotes tau hyperphosphorylation depending on the amino acids on the 301 site. Copyright (C) 2012 S. Karger AG, Basel}},
author = {{Oksman, M. and Wisman, Liselijn and Jiang, H. and Miettinen, P. and Kirik, Deniz and Tanila, H.}},
issn = {{1660-2862}},
keywords = {{Parkinson's disease; Lewy body dementia; Neurofibrillary tangles; Hippocampus; Memory}},
language = {{eng}},
number = {{2}},
pages = {{91--102}},
publisher = {{Karger}},
series = {{Neurodegenerative Diseases}},
title = {{Transduced Wild-Type but Not P301S Mutated Human Tau Shows Hyperphosphorylation in Transgenic Mice Overexpressing A30P Mutated Human Alpha-Synuclein}},
url = {{http://dx.doi.org/10.1159/000341596}},
doi = {{10.1159/000341596}},
volume = {{12}},
year = {{2013}},
}