Seizures are a druggable mechanistic link between TBI and subsequent tauopathy
Hadeel Alyenbaawi,
Richard Kanyo,
Laszlo F Locskai,
Razieh Kamali-Jamil,
Michèle G DuVal,
Qing Bai,
Holger Wille,
Edward A Burton,
W Ted Allison
Affiliations
Hadeel Alyenbaawi
Centre for Prions & Protein Folding Disease, University of Alberta, Edmonton, Canada; Department of Medical Genetics, University of Alberta, Edmonton, Canada; Majmaah University, Majmaah, Saudi Arabia
Richard Kanyo
Centre for Prions & Protein Folding Disease, University of Alberta, Edmonton, Canada; Department of Biological Sciences, University of Alberta, Edmonton, Canada
Laszlo F Locskai
Centre for Prions & Protein Folding Disease, University of Alberta, Edmonton, Canada; Department of Biological Sciences, University of Alberta, Edmonton, Canada
Razieh Kamali-Jamil
Centre for Prions & Protein Folding Disease, University of Alberta, Edmonton, Canada; Department of Biochemistry, University of Alberta, Edmonton, Canada
Centre for Prions & Protein Folding Disease, University of Alberta, Edmonton, Canada; Department of Biochemistry, University of Alberta, Edmonton, Canada
Department of Neurology, University of Pittsburgh, Pittsburgh, United States; Geriatric Research, Education and Clinical Center, Pittsburgh VA Healthcare System, Pittsburgh, United States
Centre for Prions & Protein Folding Disease, University of Alberta, Edmonton, Canada; Department of Medical Genetics, University of Alberta, Edmonton, Canada; Department of Biological Sciences, University of Alberta, Edmonton, Canada
Traumatic brain injury (TBI) is a prominent risk factor for dementias including tauopathies like chronic traumatic encephalopathy (CTE). The mechanisms that promote prion-like spreading of Tau aggregates after TBI are not fully understood, in part due to lack of tractable animal models. Here, we test the putative role of seizures in promoting the spread of tauopathy. We introduce ‘tauopathy reporter’ zebrafish expressing a genetically encoded fluorescent Tau biosensor that reliably reports accumulation of human Tau species when seeded via intraventricular brain injections. Subjecting zebrafish larvae to a novel TBI paradigm produced various TBI features including cell death, post–traumatic seizures, and Tau inclusions. Bath application of dynamin inhibitors or anticonvulsant drugs rescued TBI-induced tauopathy and cell death. These data suggest a role for seizure activity in the prion-like seeding and spreading of tauopathy following TBI. Further work is warranted regarding anti-convulsants that dampen post-traumatic seizures as a route to moderating subsequent tauopathy.
