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:

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

Acknowledgments

The authors have no competing interests to declare. The authors thank Ashley Bush, Peng Lei, and Paul Adlard from the Florey Institute of Neuroscience and Mental Health for their assistance in establishing the mouse colonies.

Declaration of interest

The authors report no conflicts of interest.

Additional information

Funding

This study was funded by an NHMRC project grant to SRS, NCJ, and TOB, as well as an NHMRC fellowship to SRS;National Health and Medical Research Council [1159645];National Health and Medical Research Council [1141643].