The Role of tau in Modulating Hyper Excitability in an Emerging Model of Tumor Associated Epilepsy
Abstract number :
3.004
Submission category :
1. Translational Research: 1A. Mechanisms / 1A1. Epileptogenesis of acquired epilepsies
Year :
2016
Submission ID :
195534
Source :
www.aesnet.org
Presentation date :
12/5/2016 12:00:00 AM
Published date :
Nov 21, 2016, 18:00 PM
Authors :
Asante Hatcher, Baylor College of Medicine; Kwanha Yu, Baylor College of Medicine; Joshua Lalonde, Baylor College of Medicine, Texas; Benjamin Deneen, Baylor College of Medicine, Houston; and Jeffrey Noebels, Baylor College of Medicine
Rationale: Hyper-excitability of neuronal networks underlies the pathophysiology of epilepsy, and is known to be a component of other neurological disorders including cancers of the brain. Previous work has shown that genetic removal of neuronal microtubule organizer and stabilizer tau can significantly reduce epileptiform activity and lethality across a number of models of hyper-excitability, including Alzheimer's Disease models, the Kcna1 early lethal mouse model of epilepsy, and the Scn1a mouse model of Dravet syndrome. We recently confirmed a progressive seizure phenotype in a novel transgenic mouse model of brain tumor associated epilepsy. The effect of tau loss on hyper-excitability and lethality in this glioblastoma model is unknown. Methods: To answer this question, we generated glial derived brain tumors on a tau knockout background using a CRISPR in uteroelectroporation strategy. Using chronic video electroencephalography (EEG), we recorded cortical inter-ictal spike and seizure activity in these tumor mice at various timepoints in disease progression, monitored survival, and assessed tumor burden via immunohistochemically methods. Results: In preliminary results, tau KO tumor mice exhibited reduced inter-ictal spike activity and slightly longer survival margins compared to tau WT tumor-bearing littermates. Conclusions: These data suggest that tau loss may provide a modest protective effect in this model of cortical hyper-excitability, and further investigation is under way to confirm these initial findings. Funding: This work was supported by grants from NIH and CPRIT (JLN, BD) (r01ns071153)
Translational Research