Abstract
Hearing impairment is the most common sensory deficit, affecting more than 400 million people worldwide. Sensorineural hearing losses currently lack any specific or efficient pharmacotherapy largely due to the insufficient knowledge of the pathomechanism. Purinergic signaling plays a substantial role in cochlear (patho)physiology. P2 (ionotropic P2X and the metabotropic P2Y) as well as adenosine receptors expressed on cochlear sensory and non-sensory cells are involved mostly in protective mechanisms of the cochlea. They are implicated in the sensitivity adjustment of the receptor cells by a K+ shunt and can attenuate the cochlear amplification by modifying cochlear micromechanics. Cochlear blood flow is also regulated by purines. Here, we propose to comprehend this field with the purine-immune interactions in the cochlea. The role of harmful immune mechanisms in sensorineural hearing losses has been emerging in the horizon of cochlear pathologies. In addition to decreasing hearing sensitivity and increasing cochlear blood supply, influencing the immune system can be the additional avenue for pharmacological targeting of purinergic signaling in the cochlea. Elucidating this complexity of purinergic effects on cochlear functions is necessary and it can result in development of new therapeutic approaches in hearing disabilities, especially in the noise-induced ones.
Highlights
The hearing organ of the mammals is located in the ossified labyrinth of the temporal bone
This review focuses on two peculiar fields: (i) The role of purinergic signaling in cochlear physiology and pathology and (ii) the description of cochlear immune system and its involvement in cochlear damage as well as their interaction, namely the role of purinergic signaling in immune system regulation in the hearing organ
We provide an overview of the purinergic signaling in the cochlea, depicting its components and P2 receptor-mediated mechanisms influencing the cochlear functions such as K+ recycling, cochlear amplification and membrane rigidity, intercellular Ca2+ waves or development of the organ of Corti
Summary
The hearing organ of the mammals is located in the ossified labyrinth of the temporal bone. IHC and OHCs: Inner and outer hair cells; SGNs: Spiral ganglion neurons; TM: Tectorial membrane. The spiral limbus the tectorial membrane (TM) overlies the hair cells, deflects their stereocilia of the OHCs thereby depolarizing or hyperpolarizing them. The lateral wall is formed by the spiral ligament containing a vascular part (stria vascularis) covered by the marginal cells. It produces the endolymph [1,5,6]. Hair cells are innervated by the spiral ganglion neurons (SGNs). More recently resident macrophages were found in several parts of the cochlea (e.g., spiral limbus, BM, cochlear lateral wall) even without any damage of the BLB [13,14]. Overview of the purinergic modulation of the immune system and the involvement of the immune mechanisms in SNHL pathology at the end of this review draw the reader’s attention to the possibility of SNHL therapy via purinergic regulation of the cochlear immune response
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