Instituto Multidisciplinario de Investigaciones Biológicas (IMIBIO-SL CONICET), Universidad Nacional de San Luis, Ejército de los Andes 950, 5700, San Luis, Argentina.
Neurochem Res. 2019 Feb;44(2):412-420. doi: 10.1007/s11064-018-2687-4. Epub 2018 Nov 28.
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 AT 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 AT receptor mRNA localized at the same area recognized by AT antibodies and anti β III-tubulin suggesting the neuronal nature of the reactive cells. Ang II AT 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. AT receptors were present at ventral cochlear nucleus and superior olivary complex, being higher at P15 and P8, respectively. We also explored the effect of prenatal administration of Ang II or PD123319 (AT antagonist) on binding of Ang II receptors at P0, P8, P15. Both treatments increased significantly the level of AT 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 AT receptors in different nuclei, the onset of audition and the establishment of neuronal circuits of the auditory pathway.
我们通过结合放射自显影术研究了在大脑发育过程中不同听觉系统核内的血管紧张素 II 受体定位。下丘（IC）是一个大型中脑结构，作为上行和下行听觉通路上的强制性突触站，在所有年龄段（P0、P8、P15、P30）均表现出高 Ang II AT 结合，在 P15 时达到最大值。这些观察结果通过 P15 时的原位杂交和免疫荧光得到了证实，证明 AT 受体 mRNA 定位于与 AT 抗体和抗 β III-微管蛋白识别的相同区域，表明反应细胞具有神经元特性。在听觉系统的所有核内，Ang II AT 受体在早期发育阶段（P0）均不存在，在 P8 时 IC 中观察到低水平。AT 受体存在于耳蜗腹核和上橄榄复合体中，分别在 P15 和 P8 时更高。我们还探讨了产前给予 Ang II 或 PD123319（AT 拮抗剂）对 P0、P8、P15 时 Ang II 受体结合的影响。两种处理均显著增加了 P0 和 P8 时 IC 中 AT 受体的水平。尽管来自 P15 动物的整个 IC 的总结合在两种处理之间没有差异，但 IC 的中央核显示出更高的结合。我们的结果支持不同核内 Ang II AT 受体更高表达的时间与听觉开始和听觉通路神经元回路建立之间的相关性。
