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Mispatterned motile cilia beating causes flow blockage in the epileptic brain

Faubel, R. J.; Feinstein, T. N.; Santos Canellas, V.; Gaesser, J.; Beluk, N. H.; Wang, Y.; Yankova, M.; King, S. M.; Karunakaran, K. B.; Ganapathiraju, M. K.; Lo, C. W.

2021-10-30 neuroscience
10.1101/2021.10.29.465023 bioRxiv
Show abstract

Beating of motile cilia at the brain ventricular surface generates rapid flow in an evolutionary conserved pattern mediating the transport of cerebrospinal fluid, but its functional importance has yet to be demonstrated. Here we show disturbance of this transport may contribute to seizure susceptibility. Mice haploinsufficient for FoxJ1, transcription factor regulating motile cilia exhibited cilia-driven flow blockage and increased seizure susceptibility. Mutations in two epilepsy-associated kinases, Cdkl5 and Yes1, in mice resulted in similar cilia-driven flow blockage and increased seizure susceptibility. We showed this arises from disorganized cilia polarity associated with disruption in the highly organized basal body anchoring meshwork. Together these findings suggest mispatterning of cilia-generated flow may contribute to epilepsy and thus might account for seizures unresponsive to current seizure medications. One sentence summaryEpilepsy is associated with disturbance of cilia motion and mispatterning of fluid transport in the brain ventricles.

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