Ablation of Liver X receptor β in mice leads to overactive macrophages and death of spiral ganglion neurons

Xiao yu Song, Wan fu Wu, Yu bing Dai, Hai wei Xu, Andrew Roman, Li Wang, Margaret Warner, Jan-Ake Gustafsson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Age-related hearing loss is the most common type of hearing impairment, and is typically characterized by the loss of spiral ganglion neurons (SGNs). The two Liver X receptors (LXRs) are oxysterol-activated nuclear receptors which in adults, regulate genes involved in cholesterol homeostasis and modulation of macrophage activity. LXRβ plays a key role in maintenance of health of dopaminergic neurons in the substantia nigra, large motor neurons in the spinal cord, and retinal ganglion cells in adult mice. We now report that LXRβ is expressed in the SGNs of the cochlea and that loss of LXRβ leads to age-related cochlea degeneration. We found that in the cochlea of LXRβ–/– mice, there is loss of SGNs, activation of macrophages, demyelination in the spiral ganglion, decrease in glutamine synthetase (GS) expression and increase in glutamate accumulation in the cochlea. Part of the cause of damage to the SGNs might be glutamate toxicity which is known to be very toxic to these cells. Our study provides a so far unreported role of LXRβ in maintenance of SGNs whose loss is a very common cause of hearing impairment.

Original languageEnglish (US)
Article number108534
JournalHearing Research
Volume422
DOIs
StatePublished - Sep 1 2022

Keywords

  • Liver X receptor
  • macrophages
  • Nuclear receptor
  • Spiral ganglion neurons

ASJC Scopus subject areas

  • Sensory Systems

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