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Pharmacological regeneration of sensory hair cells restores afferent innervation and vestibular function
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Pharmacological regeneration of sensory hair cells restores afferent innervation and vestibular function
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Journal Article
Pharmacological regeneration of sensory hair cells restores afferent innervation and vestibular function
2024
Overview
The sensory cells that transduce the signals for hearing and balance are highly specialized mechanoreceptors called hair cells that together with supporting cells comprise the sensory epithelia of the inner ear. Loss of hair cells from toxin exposure and age can cause balance disorders and is essentially irreversible due to the inability of mammalian vestibular organs to regenerate physiologically active hair cells. Here, we show substantial regeneration of hair cells in a mouse model of vestibular damage by treatment with a combination of glycogen synthase kinase 3β and histone deacetylase inhibitors. The drugs stimulated supporting cell proliferation and differentiation into hair cells. The new hair cells were reinnervated by vestibular afferent neurons, rescuing otolith function by restoring head translation-evoked otolith afferent responses and vestibuloocular reflexes. Drugs that regenerate hair cells thus represent a potential therapeutic approach to the treatment of balance disorders.
Publisher
American Society for Clinical Investigation
Subject
/ Analysis
/ Animals
/ Balance
/ Cell Differentiation - drug effects
/ Cell Proliferation - drug effects
/ Glycogen
/ Glycogen Synthase Kinase 3 - antagonists & inhibitors
/ Glycogen Synthase Kinase 3 - metabolism
/ Glycogen Synthase Kinase 3 beta - antagonists & inhibitors
/ Glycogen Synthase Kinase 3 beta - genetics
/ Glycogen Synthase Kinase 3 beta - metabolism
/ Growth
/ Hair cells (Mechanoreceptors)
/ Hair Cells, Auditory - drug effects
/ Hair Cells, Auditory - metabolism
/ Hair Cells, Vestibular - metabolism
/ Histone Deacetylase Inhibitors - pharmacology
/ Labeling
/ Mice
/ Otology
/ Toxins
