Age-Related Changes in Ang II Receptor Localization and Expression in the Developing Auditory Pathway

Abstract

We studied Ang II receptor localization in different nuclei of the auditory system, by means of binding autoradiography,during brain development. The inferior colliculus (IC), a large midbrain structure which serves as an obligatory synaptic station in both the ascending and descending auditory pathways, exhibited high Ang II AT2 binding at all ages (P0, P8,P15, P30), being maximal at P15. These observations were confirmed by in situ hybridization and immunofluorescence at P15, demonstrating that AT2 receptor mRNA localized at the same area recognized by AT2 antibodies and anti β III?tubulin suggesting the neuronal nature of the reactive cells. Ang II AT1 receptors were absent at early developmental ages (P0) in all nuclei of the auditory system and a low level was observed in the IC at the age P8. AT2 receptors were present at ventral cochlear nucleus and superior olivary complex, being higher at P15 and P8, respectively. We also explored the effect ofprenatal administration of Ang II or PD123319 (AT2 antagonist) on binding of Ang II receptors at P0, P8, P15. Both treatments increased significantly the level of AT2 receptors at P0 and P8 in the IC. Although total binding in the whole IC from P15 animals showed no difference between treatments, the central nucleus of the IC exhibited higher binding. Our results supports a correlation between the timing of the higher expression of Ang II AT2 receptors in different nuclei, the onset of audition and the establishment of neuronal circuits of the auditory pathway.