Abstracts

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 was unknown.   Methods:  To answer this question, we generated glial derived brain tumors on a tau knockout background using a CRISPR in utero electroporation strategy. Using chronic video electroencephalography (EEG), we recorded cortical inter-ictal spike and seizure activity in these tumor mice at various time points in disease progression, monitored survival, and assessed tumor burden via immunohistochemically methods. 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. Funding: HHMI Gilliam Fellowship (AH)CPRIT (BD) NIH NS29709 (JLN)