Distinct Expression Patterns of Apoptosis and Autophagy-Associated Proteins and Genes during Postnatal Development of Spiral Ganglion Neurons in Rat.

Shule Hou,Yuren Hong,Dekun Gao,Yue Li,Fabio Mammano,Huan Qin,Lianhua Sun,Jiarui Chen,Jun Yang,Penghui Chen,Jianyong Chen,Shuna Li,Baihui He,Junmin Chen,Jingchun He

doi:10.1155/2020/9387560

Abstract

Autophagy and apoptosis have a complex interplay in the early embryo development. The development of spiral ganglion neurons (SGNs) in addition to Corti's organ in the mammalian cochlea remains crucial in the first two-week postnatal period. To investigate the roles of apoptosis and autophagy in the development of SGNs, light microscopy was used to observe the morphological changes of SGNs. The number of SGNs was decreased from P1 to P7 and plateaued from P10 to P14. Immunohistochemistry results revealed positive expression of cleaved-caspase3, bcl-2, microtubule-associated protein light chain 3-II (LC3-II), Beclin1, and sequestosome 1 (SQSTM1/P62) in SGNs. The apoptotic bodies and autophagosomes and autolysosomes were also identified by transmission electron microscopy at P1 and P7. Real-time PCR and western blotting results revealed that the apoptotic activity peaked at P7 and the autophagy activity was gradually upregulated along with the development. Taken together, our results for the first time showed that autophagy and apoptosis in SGNs play distinct roles during specific developmental phases in a time-dependent manner.

Highlights

The auditory function in neonatal rats remains immature, and the cochlear structure and function gradually attain maturity by the second postnatal week
hair cells (HCs) in the cochlea play a critical role in the conversion of mechanical sound waves into neural signals, and spiral ganglion neurons (SGNs) transmit these signals to the auditory cortex for hearing
In the mammal’s inner ear, HCs and SGNs are vulnerable to multiple damages, but the regenerative ability of HCs and SGNs is limited in mammals, and so most of the damaged HCs and SGNs cannot spontaneously regenerate

Summary

Introduction

The auditory function in neonatal rats remains immature, and the cochlear structure and function gradually attain maturity by the second postnatal week. The calyx of Held gradually matures in the cochlear nucleus, thereby establishing the function of cochlear output [4] These bipolar SGNs develop long processes that connect the hair cells (HCs) in the cochlea with the neurons in the cochlear nucleus in order to process accuracy and speed required for auditory information. Apoptosis (“self-killing”) and autophagy (“self-eating”) are two self-destruction processes that play an important role in the development of inner ear. The autophagic machinery genes such as microtubule-associated protein light chain 3-II (LC3-II), Beclin, and sequestosome 1 (SQSTM1/P62) and apoptosis-related factors including bcl-2, cleaved-caspase-3, and caspase-3 were detected to investigate differential expression patterns of autophagy and apoptotic-associated proteins and genes and their putative correlation during the development of SGNs in rats in the present study

Materials and Methods

Result

Discussion

Findings

Conflicts of Interest