The University of Southampton
University of Southampton Institutional Repository

Tau protein is required for amyloid ?-induced impairment of hippocampal long-term potentiation

Tau protein is required for amyloid ?-induced impairment of hippocampal long-term potentiation
Tau protein is required for amyloid ?-induced impairment of hippocampal long-term potentiation
Amyloid ? (A?) and tau protein are both implicated in memory impairment, mild cognitive impairment (MCI), and early Alzheimer's disease (AD), but whether and how they interact is unknown. Consequently, we asked whether tau protein is required for the robust phenomenon of A?-induced impairment of hippocampal long-term potentiation (LTP), a widely accepted cellular model of memory. We used wild-type mice and mice with a genetic knock-out of tau protein and recorded field potentials in an acute slice preparation. We demonstrate that the absence of tau protein prevents A?-induced impairment of LTP. Moreover, we show that A? increases tau phosphorylation and that a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks the increased tau phosphorylation induced by A? and prevents A?-induced impairment of LTP in wild-type mice. Together, these findings show that tau protein is required for A? to impair synaptic plasticity in the hippocampus and suggest that the A?-induced impairment of LTP is mediated by tau phosphorylation. We conclude that preventing the interaction between A? and tau could be a promising strategy for treating cognitive impairment in MCI and early AD

1688-1692
Shipton, Olivia A.
a28d9db9-e5c3-4fc0-84df-26e45872552e
Leitz, Julie R.
1ce4edbc-bb00-4041-8bf2-c45625ee293a
Dworzak, Jenny
e137a174-3ddd-4b84-a3c3-dfb9335b7510
Acton, Christine E.J.
06f87e69-cd46-45a7-8215-e50b0c8d2910
Tunbridge, Elizabeth M.
f849d1cc-53c8-4af1-ad03-d3b510a49e7e
Denk, Franziska
6bbf478a-9d9a-4b27-a6c2-b529abfe4f5c
Dawson, Hana N.
a4098d5d-a388-47d5-ac1c-157b994f1657
Vitek, Michael P.
4d4f625e-4ba9-4bb7-be48-03bf29b26ef9
Wade-Martins, Richard
e04b9f70-fc8c-49b0-b994-4dd9f0cc950b
Paulsen, Ole
fb305f62-2a16-48b0-921a-2cbc59b85c1f
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
Shipton, Olivia A.
a28d9db9-e5c3-4fc0-84df-26e45872552e
Leitz, Julie R.
1ce4edbc-bb00-4041-8bf2-c45625ee293a
Dworzak, Jenny
e137a174-3ddd-4b84-a3c3-dfb9335b7510
Acton, Christine E.J.
06f87e69-cd46-45a7-8215-e50b0c8d2910
Tunbridge, Elizabeth M.
f849d1cc-53c8-4af1-ad03-d3b510a49e7e
Denk, Franziska
6bbf478a-9d9a-4b27-a6c2-b529abfe4f5c
Dawson, Hana N.
a4098d5d-a388-47d5-ac1c-157b994f1657
Vitek, Michael P.
4d4f625e-4ba9-4bb7-be48-03bf29b26ef9
Wade-Martins, Richard
e04b9f70-fc8c-49b0-b994-4dd9f0cc950b
Paulsen, Ole
fb305f62-2a16-48b0-921a-2cbc59b85c1f
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1

Shipton, Olivia A., Leitz, Julie R., Dworzak, Jenny, Acton, Christine E.J., Tunbridge, Elizabeth M., Denk, Franziska, Dawson, Hana N., Vitek, Michael P., Wade-Martins, Richard, Paulsen, Ole and Vargas-Caballero, Mariana (2011) Tau protein is required for amyloid ?-induced impairment of hippocampal long-term potentiation. Journal of Neuroscience, 31 (5), 1688-1692. (doi:10.1523/JNEUROSCI.2610-10.2011).

Record type: Article

Abstract

Amyloid ? (A?) and tau protein are both implicated in memory impairment, mild cognitive impairment (MCI), and early Alzheimer's disease (AD), but whether and how they interact is unknown. Consequently, we asked whether tau protein is required for the robust phenomenon of A?-induced impairment of hippocampal long-term potentiation (LTP), a widely accepted cellular model of memory. We used wild-type mice and mice with a genetic knock-out of tau protein and recorded field potentials in an acute slice preparation. We demonstrate that the absence of tau protein prevents A?-induced impairment of LTP. Moreover, we show that A? increases tau phosphorylation and that a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks the increased tau phosphorylation induced by A? and prevents A?-induced impairment of LTP in wild-type mice. Together, these findings show that tau protein is required for A? to impair synaptic plasticity in the hippocampus and suggest that the A?-induced impairment of LTP is mediated by tau phosphorylation. We conclude that preventing the interaction between A? and tau could be a promising strategy for treating cognitive impairment in MCI and early AD

Text
__soton.ac.uk_ude_PersonalFiles_Users_db5_mydesktop_Tau_protein_is_required_for_amyloid_2011.pdf - Version of Record
Download (838kB)

More information

Published date: February 2011
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 348172
URI: http://eprints.soton.ac.uk/id/eprint/348172
PURE UUID: 13f03946-8887-4b2e-8950-f95fbb1556b4
ORCID for Mariana Vargas-Caballero: ORCID iD orcid.org/0000-0003-2326-4001

Catalogue record

Date deposited: 08 Feb 2013 11:54
Last modified: 17 Dec 2019 01:38

Export record

Altmetrics

Contributors

Author: Olivia A. Shipton
Author: Julie R. Leitz
Author: Jenny Dworzak
Author: Christine E.J. Acton
Author: Elizabeth M. Tunbridge
Author: Franziska Denk
Author: Hana N. Dawson
Author: Michael P. Vitek
Author: Richard Wade-Martins
Author: Ole Paulsen

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×