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Subacute Changes in Cleavage Processing of Amyloid Precursor Protein and Tau following Penetrating Traumatic Brain Injury

Traumatic brain injury (TBI) is an established risk factor for the development of Alzheimer’s disease (AD). Here the effects of severe penetrating TBI on APP and tau cleavage processing were investigated in a rodent model of penetrating ballistic-like brain injury (PBBI). PBBI was induced by stereot...

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Autores principales: Cartagena, Casandra M., Mountney, Andrea, Hwang, Hye, Swiercz, Adam, Rammelkamp, Zoe, Boutte, Angela M., Shear, Deborah A., Tortella, Frank C., Schmid, Kara E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948774/
https://www.ncbi.nlm.nih.gov/pubmed/27428544
http://dx.doi.org/10.1371/journal.pone.0158576
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author Cartagena, Casandra M.
Mountney, Andrea
Hwang, Hye
Swiercz, Adam
Rammelkamp, Zoe
Boutte, Angela M.
Shear, Deborah A.
Tortella, Frank C.
Schmid, Kara E.
author_facet Cartagena, Casandra M.
Mountney, Andrea
Hwang, Hye
Swiercz, Adam
Rammelkamp, Zoe
Boutte, Angela M.
Shear, Deborah A.
Tortella, Frank C.
Schmid, Kara E.
author_sort Cartagena, Casandra M.
collection PubMed
description Traumatic brain injury (TBI) is an established risk factor for the development of Alzheimer’s disease (AD). Here the effects of severe penetrating TBI on APP and tau cleavage processing were investigated in a rodent model of penetrating ballistic-like brain injury (PBBI). PBBI was induced by stereotactically inserting a perforated steel probe through the right frontal cortex of the anesthetized rat and rapidly inflating/deflating the probe’s elastic tubing into an elliptical shaped balloon to 10% of total rat brain volume causing temporary cavitation injury. Separate animals underwent probe injury (PrI) alone without balloon inflation. Shams underwent craniectomy. Brain tissue was collected acutely (4h, 24h, 3d) and subacutely (7d) post-injury and analyzed by immunoblot for full length APP (APP-FL) and APP beta c-terminal fragments (βCTFs), full length tau (tau-FL) and tau truncation fragments and at 7d for cytotoxic Beta amyloid (Aβ) peptides Aβ40 and Aβ42 analysis. APP-FL was significantly decreased at 3d and 7d following PBBI whereas APP βCTFs were significantly elevated by 4h post-injury and remained elevated through 7d post-injury. Effects on βCTFs were mirrored with PrI, albeit to a lesser extent. Aβ40 and Aβ42 were significantly elevated at 7d following PBBI and PrI. Tau-FL decreased substantially 3d and 7d post-PBBI and PrI. Importantly, a 22 kDa tau fragment (tau22), similar to that found in AD, was significantly elevated by 4h and remained elevated through 7d post-injury. Thus both APP and tau cleavage was dramatically altered in the acute and subacute periods post-injury. As cleavage of these proteins has also been implicated in AD, TBI pathology shown here may set the stage for the later development of AD or other tauopathies.
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spelling pubmed-49487742016-08-01 Subacute Changes in Cleavage Processing of Amyloid Precursor Protein and Tau following Penetrating Traumatic Brain Injury Cartagena, Casandra M. Mountney, Andrea Hwang, Hye Swiercz, Adam Rammelkamp, Zoe Boutte, Angela M. Shear, Deborah A. Tortella, Frank C. Schmid, Kara E. PLoS One Research Article Traumatic brain injury (TBI) is an established risk factor for the development of Alzheimer’s disease (AD). Here the effects of severe penetrating TBI on APP and tau cleavage processing were investigated in a rodent model of penetrating ballistic-like brain injury (PBBI). PBBI was induced by stereotactically inserting a perforated steel probe through the right frontal cortex of the anesthetized rat and rapidly inflating/deflating the probe’s elastic tubing into an elliptical shaped balloon to 10% of total rat brain volume causing temporary cavitation injury. Separate animals underwent probe injury (PrI) alone without balloon inflation. Shams underwent craniectomy. Brain tissue was collected acutely (4h, 24h, 3d) and subacutely (7d) post-injury and analyzed by immunoblot for full length APP (APP-FL) and APP beta c-terminal fragments (βCTFs), full length tau (tau-FL) and tau truncation fragments and at 7d for cytotoxic Beta amyloid (Aβ) peptides Aβ40 and Aβ42 analysis. APP-FL was significantly decreased at 3d and 7d following PBBI whereas APP βCTFs were significantly elevated by 4h post-injury and remained elevated through 7d post-injury. Effects on βCTFs were mirrored with PrI, albeit to a lesser extent. Aβ40 and Aβ42 were significantly elevated at 7d following PBBI and PrI. Tau-FL decreased substantially 3d and 7d post-PBBI and PrI. Importantly, a 22 kDa tau fragment (tau22), similar to that found in AD, was significantly elevated by 4h and remained elevated through 7d post-injury. Thus both APP and tau cleavage was dramatically altered in the acute and subacute periods post-injury. As cleavage of these proteins has also been implicated in AD, TBI pathology shown here may set the stage for the later development of AD or other tauopathies. Public Library of Science 2016-07-18 /pmc/articles/PMC4948774/ /pubmed/27428544 http://dx.doi.org/10.1371/journal.pone.0158576 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Cartagena, Casandra M.
Mountney, Andrea
Hwang, Hye
Swiercz, Adam
Rammelkamp, Zoe
Boutte, Angela M.
Shear, Deborah A.
Tortella, Frank C.
Schmid, Kara E.
Subacute Changes in Cleavage Processing of Amyloid Precursor Protein and Tau following Penetrating Traumatic Brain Injury
title Subacute Changes in Cleavage Processing of Amyloid Precursor Protein and Tau following Penetrating Traumatic Brain Injury
title_full Subacute Changes in Cleavage Processing of Amyloid Precursor Protein and Tau following Penetrating Traumatic Brain Injury
title_fullStr Subacute Changes in Cleavage Processing of Amyloid Precursor Protein and Tau following Penetrating Traumatic Brain Injury
title_full_unstemmed Subacute Changes in Cleavage Processing of Amyloid Precursor Protein and Tau following Penetrating Traumatic Brain Injury
title_short Subacute Changes in Cleavage Processing of Amyloid Precursor Protein and Tau following Penetrating Traumatic Brain Injury
title_sort subacute changes in cleavage processing of amyloid precursor protein and tau following penetrating traumatic brain injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948774/
https://www.ncbi.nlm.nih.gov/pubmed/27428544
http://dx.doi.org/10.1371/journal.pone.0158576
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