The developmental expression and distribution of adenosine receptors in the mouse cochlea

Abstract

Adenosine is an important endogenous purine nucleoside that acts as a neuromodulator regulating cellular activity in the central nervous system and peripheral organs. During cellular stress responses, such as hypoxia, ischemia and inflammation, adenosine is released from cells and is believed to act in a cytoprotective manner via high affinity adenosine receptors. The expression and distribution of adenosine receptors has been recently characterised in the adult rat inner ear, but there is no information about the distribution of these receptors in the developing mammalian cochlea. To close this knowledge gap, the present study investigated the distribution patterns of adenosine A1, A2A and A3 receptors (R) in the developing and adult mouse cochlea. Cochlear tissues were removed from mice at different postnatal ages: P0, P4, P8, P12, P21 and also 6-8 week adults, fixed in 4% paraformaldehyde, cryosectioned then processed for adenosine receptor immunohistochemistry. Sections were studied by laser scanning confocal microscopy. We have observed an age-dependant expression pattern of both A2AR and A3R in the mouse cochlea, however the A1R pattern was inconclusive due to antibody specificity issues. A2AR was detected for the first time from the onset of hearing (P12) in the developing cochlea, with expression in the blood vessels of the modiolus and spiral ligament. A3R was expressed extensively from birth throughout the cochlea, including the sensory cells and their synaptic regions, stria vascularis, spiral ganglion and associated nerve fibres. Sub cellular localisation of A3R changed during cochlear development, from mostly cytoplasmic in the juvenile cochlea to membrane bound after the onset of hearing. This study provides novel findings of A2AR and A3R distribution in the developing and adult mouse cochlea. Given previous observations on the distribution of P2 (ATP) receptors in the developing cochlea, our results suggest that adenosine receptor signalling in the developing mammalian inner ear works closely with P2 (ATP) receptor signalling to provide an optimal environment for a number of important physiological functions in the inner ear. This study thus underlines an important role of purinergic signalling in cochlear development and physiology.