Identification of Compounds that Modulate Ependymal Cell Cilia Beat Frequency
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Date
2025-05
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The Ohio State University
Abstract
Ependymal cells line the ventricles of the central nervous system and contain motile cilia that project into the cerebrospinal fluid. The beating of these cilia is thought to contribute to the circulation and flow patterns of cerebrospinal fluid. Abnormalities to cerebrospinal fluid flow and defects to ependymal cilia are linked to a variety of conditions such as hydrocephalus, mood disorders and traumatic brain injury. Altering cilia beat frequency and the flow patterns of the cerebrospinal fluid would allow for more comprehensive pathophysiological studies to be conducted on the role that flow networks and cilia play in these conditions. However, there is no comprehensive list of compounds that alter ependymal cell cilia beating. Here, we use agonists of identified G-protein coupled receptors to identify novel compounds that alter ependymal ciliary beating. We show that the application of adenosine and norepinephrine increase the frequency of ependymal cell ciliary beating, GABA has a null effect, and endothelin-1 can decrease cilia beating. Additionally, we show that there is variance in the normal beat frequency of cilia between the lateral ventricle and dorsal 3rd ventricle, suggesting there may be differences in how compounds interact with cilia within specific ventricles. Given this data and existing literature, we hypothesize that ependymal cells contain sensory signaling systems that modulate ciliary beat frequency through complex mechanisms likely involving the activation of PKA from increased levels of cAMP.