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Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex

Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex
Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex
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.

1078-8956
1325-1332
Liu, Xue Jun
0892d8c8-7208-46f6-b7a6-c15751a6d67b
Gingrich, Jeffrey R
f60e5843-939c-4fe8-afb5-cdc0d751ec98
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
Dong, Yi Na
cfa6dc61-2a70-4832-8d5a-cc1e35192e35
Sengar, Ameet
b0aef6a6-ce12-46ce-8bec-d9e7cb6550b7
Beggs, Simon
b1530e2f-9f7c-41a9-a9dc-bafd53403615
Wang, Szu-Han
cccd814b-1065-46c9-a68d-d8cf52a51e40
Ding, Hoi Ki
dad850c0-e902-4d43-9a0c-25e63b8238ca
Frankland, Paul W
d0e82e32-6aca-4a86-86c7-f3bf418d9752
Salter, Michael W
05401612-950d-45e8-b29e-cd25b15d33eb
Liu, Xue Jun
0892d8c8-7208-46f6-b7a6-c15751a6d67b
Gingrich, Jeffrey R
f60e5843-939c-4fe8-afb5-cdc0d751ec98
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
Dong, Yi Na
cfa6dc61-2a70-4832-8d5a-cc1e35192e35
Sengar, Ameet
b0aef6a6-ce12-46ce-8bec-d9e7cb6550b7
Beggs, Simon
b1530e2f-9f7c-41a9-a9dc-bafd53403615
Wang, Szu-Han
cccd814b-1065-46c9-a68d-d8cf52a51e40
Ding, Hoi Ki
dad850c0-e902-4d43-9a0c-25e63b8238ca
Frankland, Paul W
d0e82e32-6aca-4a86-86c7-f3bf418d9752
Salter, Michael W
05401612-950d-45e8-b29e-cd25b15d33eb

Liu, Xue Jun, Gingrich, Jeffrey R, Vargas-Caballero, Mariana, Dong, Yi Na, Sengar, Ameet, Beggs, Simon, Wang, Szu-Han, Ding, Hoi Ki, Frankland, Paul W and Salter, Michael W (2008) Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex. Nature Medicine, 14 (12), 1325-1332. (doi:10.1038/nm.1883). (PMID:19011637)

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.

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More information

e-pub ahead of print date: 16 November 2008
Published date: December 2008
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 348178
URI: http://eprints.soton.ac.uk/id/eprint/348178
ISSN: 1078-8956
PURE UUID: 4f80eaaf-dd73-43b7-83dd-df57fe7f8177
ORCID for Mariana Vargas-Caballero: ORCID iD orcid.org/0000-0003-2326-4001

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Date deposited: 08 Feb 2013 15:14
Last modified: 10 Jan 2022 02:59

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Contributors

Author: Xue Jun Liu
Author: Jeffrey R Gingrich
Author: Yi Na Dong
Author: Ameet Sengar
Author: Simon Beggs
Author: Szu-Han Wang
Author: Hoi Ki Ding
Author: Paul W Frankland
Author: Michael W Salter

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