PUBLICATION
Seizures are a druggable mechanistic link between TBI and subsequent tauopathy
- Authors
- Alyenbaawi, H., Kanyo, R., Locskai, L.F., Kamali-Jamil, R., DuVal, M.G., Bai, Q., Wille, H., Burton, E.A., Allison, W.T.
- ID
- ZDB-PUB-210203-7
- Date
- 2021
- Source
- eLIFE 10: (Journal)
- Registered Authors
- Allison, Ted, Burton, Edward A., Duval, Michèle
- Keywords
- anti-epileptics, epilepsy, neuroscience, neurotrauma, post-traumatic seizures, tauopathy, traumatic brain injury, zebrafish
- MeSH Terms
-
- tau Proteins/metabolism
- Brain Injuries, Traumatic/complications*
- Larva
- Zebrafish
- Mice
- Cell Death/drug effects
- Seizures/complications*
- Seizures/drug therapy
- Dynamins/antagonists & inhibitors
- Green Fluorescent Proteins/genetics
- Tauopathies/drug therapy*
- Tauopathies/etiology
- Anticonvulsants/pharmacology
- Animals
- Animals, Genetically Modified
- PubMed
- 33527898 Full text @ Elife
Citation
Alyenbaawi, H., Kanyo, R., Locskai, L.F., Kamali-Jamil, R., DuVal, M.G., Bai, Q., Wille, H., Burton, E.A., Allison, W.T. (2021) Seizures are a druggable mechanistic link between TBI and subsequent tauopathy. eLIFE. 10:.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping