Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury
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 m...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/11/9439 |
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| author | Wai Hang Cheng Honor Cheung Amy Kang Jianjia Fan Jennifer Cooper Mehwish Anwer Carlos Barron Anna Wilkinson Grace Hu Jefferey Yue Peter A. Cripton David J. Vocadlo Cheryl L. Wellington |
| author_facet | Wai Hang Cheng Honor Cheung Amy Kang Jianjia Fan Jennifer Cooper Mehwish Anwer Carlos Barron Anna Wilkinson Grace Hu Jefferey Yue Peter A. Cripton David J. Vocadlo Cheryl L. Wellington |
| author_sort | Wai Hang Cheng |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T03:05:56Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:05:56Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b3225a633fe0463c907c7ecebeacbbc02023-11-18T07:59:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012411943910.3390/ijms24119439Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain InjuryWai Hang Cheng0Honor Cheung1Amy Kang2Jianjia Fan3Jennifer Cooper4Mehwish Anwer5Carlos Barron6Anna Wilkinson7Grace Hu8Jefferey Yue9Peter A. Cripton10David J. Vocadlo11Cheryl L. Wellington12Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Chemistry, Simon Fraser University, Vancouver, BC V5A 1S6, CanadaDjavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDepartment of Chemistry, Simon Fraser University, Vancouver, BC V5A 1S6, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaTraumatic 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.https://www.mdpi.com/1422-0067/24/11/9439traumatic brain injuryGSK-3βtauopathyCHIMERA |
| spellingShingle | Wai Hang Cheng Honor Cheung Amy Kang Jianjia Fan Jennifer Cooper Mehwish Anwer Carlos Barron Anna Wilkinson Grace Hu Jefferey Yue Peter A. Cripton David J. Vocadlo Cheryl L. Wellington Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury International Journal of Molecular Sciences traumatic brain injury GSK-3β tauopathy CHIMERA |
| title | Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury |
| title_full | Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury |
| title_fullStr | Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury |
| title_full_unstemmed | Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury |
| title_short | Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury |
| title_sort | altered tau kinase activity in rtg4510 mice after a single interfaced chimera traumatic brain injury |
| topic | traumatic brain injury GSK-3β tauopathy CHIMERA |
| url | https://www.mdpi.com/1422-0067/24/11/9439 |
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