Evaluation of the Neurogenic Potential in the Rat Inferior Colliculus from Early Postnatal Days Until Adulthood

Jonas Engert,Kristen Rak,Miriam Scholl,Johannes Voelker,Rudolf Hagen,Linda Bieniussa

doi:10.1007/s12035-020-02151-6

Abstract

Neural stem cells (NSCs) have been recently identified in the inferior colliculus (IC). These cells are of particular interest, as no casual therapeutic options for impaired neural structures exist. This research project aims to evaluate the neurogenic potential in the rat IC from early postnatal days until adulthood. The IC of rats from postnatal day 6 up to 48 was examined by neurosphere assays and histological sections. In free-floating IC cell cultures, neurospheres formed from animals from early postnatal to adulthood. The amount of generated neurospheres decreased in older ages and increased with the number of cell line passages. Cells in the neurospheres and the histological sections stained positively with NSC markers (Doublecortin, Sox-2, Musashi-1, Nestin, and Atoh1). Dissociated single cells from the neurospheres differentiated and were stained positively for the neural lineage markers β-III-tubulin, glial fibrillary acidic protein, and myelin basic protein. In addition, NSC markers (Doublecortin, Sox-2, CDK5R1, and Ascl-1) were investigated by qRT-PCR. In conclusion, a neurogenic potential in the rat IC was detected and evaluated from early postnatal days until adulthood. The identification of NSCs in the rat IC and their age-specific characteristics contribute to a better understanding of the development and the plasticity of the auditory pathway and might be activated for therapeutic use.

Highlights

Neurogenesis is the formation of new nerve cells from precursor and stem cells, which takes place both during embryogenesis and in some regions of the adult nervous system
The expression of Atoh-1 in the cochlear nucleus decreased significantly with increasing age [27]. These results show that the neurospheres developed from the isolated cells of the inferior colliculus (IC) in all age groups studied contain cells that are positive for different stem cell and progenitor markers, and that the expression of these markers follows age-related patterns
The ability of mitotic self-renewal and proliferation and the ability to differentiate into neural progenitor cells and all cell types of the neuroectodermal cell lines were demonstrated in cells isolated from the rat IC

Summary

Introduction

Neurogenesis is the formation of new nerve cells from precursor and stem cells, which takes place both during embryogenesis and in some regions of the adult nervous system. Following the discovery of adult neurogenesis in the subventricular zone [1] and the dentate gyrus of the hippocampus [2], these brain regions were intensively investigated regarding their neurogenic potential. The existence of neural stem cells (NSC) has been demonstrated in further parts of the mammalian central nervous system, such as the cortex [3], the striatum [4], the septum [4], the spinal cord [5], the dorsal vagal complex [6], and the optic nerve [3]. Neurogenic niches were found in the centrally located parts of the auditory pathway. A stem cell potential of the cochlear nucleus (CN) was found in both rats [12] and mice [13]

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