accelerated tauopathy in the retina of transgenic P301S tau mice exposed to
repetitive mild traumatic brain injury
P, Hitt D, Marsh-Armstrong N, Koliatsos VE. Exp Neurol. 2015; ahead of print.
injury (mTBI) accelerates tauopathy among
mice genetically predisposed to tau build up.
recent years, we’ve heard about the possible relationship between repetitive
mild traumatic brain injury (mTBI) within contact and collision sports and chronic traumatic encephalopathy (CTE) – an aggregation of the protein tau in tangles or tauopathy. However, not all
exposed athletes develop this condition. Thus, genetic factors may play a role
in the risk of developing CTE because genes code for proteins (for example, tau
protein) that respond to mechanical stress. Therefore, the authors tested
whether mice, who were prone to tauopathy because of changes in the tau gene,
would experience accelerated onset of tauopathy after mTBI. The authors used 5-week old (adolescent to
young adult age) mice. These mice were exposed to different mTBI regimens: single
head impact, 4 head impacts (4 impacts on 4 separate days), 12 head impacts (3
repetitive impacts on 4 different days), or no head impacts (control). Four
mice were included in each group. The authors measured neurological function
using the neurological severity score, which uses a 10-point scale system to assess
neurobehavioral outcomes in rodents after a brain injury. Once the mouse
completed his/her head impact protocol the authors dissected and preserved brain
tissues to observe differences between groups. Among mice susceptible to
tauopathy, the density of tau in a vulnerable region increased 20 fold with one
mTBI hit, over 50 fold with 4 mTBI hits, and 60 fold with 12 mTBI hits compared
with susceptible mice without an mTBI. There was very little tau observed in
the vulnerable region in sham mice compared with those in the injured groups.
There were no differences in tau build up in the cerebral cortex (a region not
commonly affected with tauopathy) between the 4-impact and 12-impact regimen
groups. The number of hits was a factor related to tauopathy. The authors had
previously demonstrated that mice, who are not genetically predisposed to
tauopathy, lack evidence of tauopathy after mTBI.
susceptible to tauopathy a single mTBI event may have an effect on the
progression of tauopathy, but repetitive injury has an even greater effect. The
absence of an excessive buildup of tau in cortex between sham and mTBI groups
may suggest that the accelerated tauopathy after repetitive mTBI is not a
generic property of the susceptible brain. Instead it may be tied to brain
regions undergoing more stress. The authors demonstrated that mice genetically
prone to tau buildup develop higher amounts of tau, especially with more head
impacts. Determining genetic risk factors could help develop therapeutic agents
to alter tau buildup and help us council athletes who are genetically susceptible
for diseases associated with repetitive head impacts such as CTE. At this time,
medical professionals need to be aware of the risks of repetitive head impacts,
and educate their athletes about the risks like CTE. This study is a nice
reminder that not everyone will get CTE but it is critical that we discover why
some patients do.
When you educate athletes about concussion, do you mention long-term problems
like CTE? Do you think athletes would be more likely to report head impacts if
they knew it could lead to a long-term disease like CTE?
by: Jane McDevitt, PhD
by: Jeff Driban
Xu L, Ryu J, Nguyen JV, Arena J, Rha E, Vranis P, Hitt D, Marsh-Armstrong N, & Koliatsos VE (2015). Evidence for accelerated tauopathy in the retina of transgenic P301S tau mice exposed to repetitive mild traumatic brain injury. Experimental Neurology, 273, 168-176 PMID: 26311071