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Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury Cheng, Wai Hang; Cheung, Honor; Kang, Amy; Fan, Jianjia; Cooper, Jennifer; Anwer, Mehwish; Barron, Carlos; Wilkinson, Anna; Hu, Grace; Yue, Jefferey; Cripton, Peter Alec, 1965-; Vocadlo, David J.; Wellington, Cheryl L.

Abstract

Traumatic brain injury (TBI) is an established risk factor for neurodegenerative diseases. In this study, we used the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) to investigate the effects of a single high-energy TBI in rTg4510 mice, a mouse model of tauopathy. Fifteen male rTg4510 mice (4 mo) were impacted at 4.0 J using interfaced CHIMERA and were compared to sham controls. Immediately after injury, the TBI mice showed significant mortality (7/15; 47%) and a prolonged duration of loss of the righting reflex. At 2 mo post-injury, surviving mice displayed significant microgliosis (Iba1) and axonal injury (Neurosilver). Western blotting indicated a reduced p-GSK-3β (S9):GSK-3β ratio in TBI mice, suggesting chronic activation of tau kinase. Although longitudinal analysis of plasma total tau suggested that TBI accelerates the appearance of tau in the circulation, there were no significant differences in brain total or p-tau levels, nor did we observe evidence of enhanced neurodegeneration in TBI mice compared to sham mice. In summary, we showed that a single high-energy head impact induces chronic white matter injury and altered GSK-3β activity without an apparent change in post-injury tauopathy in rTg4510 mice.

Item Metadata

Title
Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury
Creator
Cheng, Wai Hang; Cheung, Honor; Kang, Amy; Fan, Jianjia; Cooper, Jennifer; Anwer, Mehwish; Barron, Carlos; Wilkinson, Anna; Hu, Grace; Yue, Jefferey; Cripton, Peter Alec, 1965-; Vocadlo, David J.; Wellington, Cheryl L.
Contributor
Djavad Mowafaghian Centre for Brain Health; International Collaboration on Repair Discoveries
Publisher
Multidisciplinary Digital Publishing Institute
Date Issued
2023-05-29
Description
Traumatic brain injury (TBI) is an established risk factor for neurodegenerative diseases. In this study, we used the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) to investigate the effects of a single high-energy TBI in rTg4510 mice, a mouse model of tauopathy. Fifteen male rTg4510 mice (4 mo) were impacted at 4.0 J using interfaced CHIMERA and were compared to sham controls. Immediately after injury, the TBI mice showed significant mortality (7/15; 47%) and a prolonged duration of loss of the righting reflex. At 2 mo post-injury, surviving mice displayed significant microgliosis (Iba1) and axonal injury (Neurosilver). Western blotting indicated a reduced p-GSK-3β (S9):GSK-3β ratio in TBI mice, suggesting chronic activation of tau kinase. Although longitudinal analysis of plasma total tau suggested that TBI accelerates the appearance of tau in the circulation, there were no significant differences in brain total or p-tau levels, nor did we observe evidence of enhanced neurodegeneration in TBI mice compared to sham mice. In summary, we showed that a single high-energy head impact induces chronic white matter injury and altered GSK-3β activity without an apparent change in post-injury tauopathy in rTg4510 mice.
Subject
traumatic brain injury; GSK-3β; tauopathy; CHIMERA
Genre
Article
Type
Text
Language
eng
Date Available
2023-08-04
Provider
Vancouver : University of British Columbia Library
Rights
CC BY 4.0
DOI
10.14288/1.0435077
URI
http://hdl.handle.net/2429/85397
Affiliation
Applied Science, Faculty of; Medicine, Faculty of; Other UBC; Non UBC; Biomedical Engineering, School of; Pathology and Laboratory Medicine, Department of
Citation
Cheng, W.H.; Cheung, H.; Kang, A.; Fan, J.; Cooper, J.; Anwer, M.; Barron, C.; Wilkinson, A.; Hu, G.; Yue, J.; et al. Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury. Int. J. Mol. Sci. 2023, 24, 9439
Publisher DOI
10.3390/ijms24119439
Peer Review Status
Reviewed
Scholarly Level
Faculty; Researcher; Postdoctoral; Graduate
Rights URI
https://creativecommons.org/licenses/by/4.0/
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CC BY 4.0