The genetic ablation of tau improves long-term, but not short-term, functional outcomes after experimental traumatic brain injury in mice

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Primary Objective: This study characterized the acute and chronic effects of tau reduction in traumatic brain injury (TBI). Research Design: A fluid percussion injury (FPI) or a sham-injury was administered to wild type (WT) or tau knockout (Tau-/-) mice. Mice were assigned to a one-week or twelve-week recovery period before behavioral testing and analysis of brain tissue. Methods and Procedures: Mice were tested on the elevated-plus maze, the Y-maze, and rotarod. The twelve-week recovery mice underwent in vivo MRI. Phosphorylated tau in brain tissue was analyzed post-mortem using western blots. Main Outcomes and Results: FPI mice, regardless of genotype, had abnormalities on the elevated-plus maze (a task to assess anxiety-like behavior) at one-week post-injury. However, after twelve-weeks recovery, the Tau-/- mice that were given an FPI were less anxious and had improved motor function compared to their WT counterparts. MRI analysis found that while all FPI mice had brain damage, the Tau-/- mice had larger hippocampal volumes. The WT+FPI mice also had increased phosphorylated tau compared to WT+sham mice at both the one-week and twelve-week recovery times. Conclusion: These findings suggest that tau may play an important role in some of the consequences of TBI, particularly the long-term functional deficits.

Original languageEnglish
Pages (from-to)131–139
Number of pages9
JournalBrain Injury
Volume34
Issue number1
DOIs
Publication statusPublished - 2020

Keywords

  • animal model
  • behavior
  • fluid percussion injury
  • mice
  • MRI
  • Traumatic brain injury

Cite this

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title = "The genetic ablation of tau improves long-term, but not short-term, functional outcomes after experimental traumatic brain injury in mice",
abstract = "Primary Objective: This study characterized the acute and chronic effects of tau reduction in traumatic brain injury (TBI). Research Design: A fluid percussion injury (FPI) or a sham-injury was administered to wild type (WT) or tau knockout (Tau-/-) mice. Mice were assigned to a one-week or twelve-week recovery period before behavioral testing and analysis of brain tissue. Methods and Procedures: Mice were tested on the elevated-plus maze, the Y-maze, and rotarod. The twelve-week recovery mice underwent in vivo MRI. Phosphorylated tau in brain tissue was analyzed post-mortem using western blots. Main Outcomes and Results: FPI mice, regardless of genotype, had abnormalities on the elevated-plus maze (a task to assess anxiety-like behavior) at one-week post-injury. However, after twelve-weeks recovery, the Tau-/- mice that were given an FPI were less anxious and had improved motor function compared to their WT counterparts. MRI analysis found that while all FPI mice had brain damage, the Tau-/- mice had larger hippocampal volumes. The WT+FPI mice also had increased phosphorylated tau compared to WT+sham mice at both the one-week and twelve-week recovery times. Conclusion: These findings suggest that tau may play an important role in some of the consequences of TBI, particularly the long-term functional deficits.",
keywords = "animal model, behavior, fluid percussion injury, mice, MRI, Traumatic brain injury",
author = "Tan, {Xin Lin} and Ping Zheng and Wright, {David K.} and Mujun Sun and Brady, {Rhys D.} and Shijie Liu and McDonald, {Stuart J.} and Richelle Mychasiuk and Sitare Cenap and Jones, {Nigel C.} and O’Brien, {Terence J.} and Shultz, {Sandy R.}",
year = "2020",
doi = "10.1080/02699052.2019.1667539",
language = "English",
volume = "34",
pages = "131–139",
journal = "Brain Injury",
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T1 - The genetic ablation of tau improves long-term, but not short-term, functional outcomes after experimental traumatic brain injury in mice

AU - Tan, Xin Lin

AU - Zheng, Ping

AU - Wright, David K.

AU - Sun, Mujun

AU - Brady, Rhys D.

AU - Liu, Shijie

AU - McDonald, Stuart J.

AU - Mychasiuk, Richelle

AU - Cenap, Sitare

AU - Jones, Nigel C.

AU - O’Brien, Terence J.

AU - Shultz, Sandy R.

PY - 2020

Y1 - 2020

N2 - Primary Objective: This study characterized the acute and chronic effects of tau reduction in traumatic brain injury (TBI). Research Design: A fluid percussion injury (FPI) or a sham-injury was administered to wild type (WT) or tau knockout (Tau-/-) mice. Mice were assigned to a one-week or twelve-week recovery period before behavioral testing and analysis of brain tissue. Methods and Procedures: Mice were tested on the elevated-plus maze, the Y-maze, and rotarod. The twelve-week recovery mice underwent in vivo MRI. Phosphorylated tau in brain tissue was analyzed post-mortem using western blots. Main Outcomes and Results: FPI mice, regardless of genotype, had abnormalities on the elevated-plus maze (a task to assess anxiety-like behavior) at one-week post-injury. However, after twelve-weeks recovery, the Tau-/- mice that were given an FPI were less anxious and had improved motor function compared to their WT counterparts. MRI analysis found that while all FPI mice had brain damage, the Tau-/- mice had larger hippocampal volumes. The WT+FPI mice also had increased phosphorylated tau compared to WT+sham mice at both the one-week and twelve-week recovery times. Conclusion: These findings suggest that tau may play an important role in some of the consequences of TBI, particularly the long-term functional deficits.

AB - Primary Objective: This study characterized the acute and chronic effects of tau reduction in traumatic brain injury (TBI). Research Design: A fluid percussion injury (FPI) or a sham-injury was administered to wild type (WT) or tau knockout (Tau-/-) mice. Mice were assigned to a one-week or twelve-week recovery period before behavioral testing and analysis of brain tissue. Methods and Procedures: Mice were tested on the elevated-plus maze, the Y-maze, and rotarod. The twelve-week recovery mice underwent in vivo MRI. Phosphorylated tau in brain tissue was analyzed post-mortem using western blots. Main Outcomes and Results: FPI mice, regardless of genotype, had abnormalities on the elevated-plus maze (a task to assess anxiety-like behavior) at one-week post-injury. However, after twelve-weeks recovery, the Tau-/- mice that were given an FPI were less anxious and had improved motor function compared to their WT counterparts. MRI analysis found that while all FPI mice had brain damage, the Tau-/- mice had larger hippocampal volumes. The WT+FPI mice also had increased phosphorylated tau compared to WT+sham mice at both the one-week and twelve-week recovery times. Conclusion: These findings suggest that tau may play an important role in some of the consequences of TBI, particularly the long-term functional deficits.

KW - animal model

KW - behavior

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