Tau phosphorylation and cochlear apoptosis cause hearing loss in 3×Tg-AD Mouse Model of Alzheimer's Disease

Sheue Er Wang, Chung Hsin Wu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Clinically typical dementia Alzheimer's disease (AD) is associated with abnormal auditory processing. However, possible molecular mechanisms responsible for the auditory pathology of AD patients are not known. According to our past research findings that the thresholds of auditory brainstem response, but not distortion product otoacoustic emissions, were significantly increased in AD mice from 9 months of age and thereafter. Thus, we further explored the possible mechanism of auditory degradation of 3×Tg-AD mice in this study. Our histochemical staining evidence showed the cochlear spiral ganglion neurons (SGN), but not the cochlear hair cells, were lost significantly in the cochlea of 3×Tg-AD mice from 9 months of age and thereafter. Our immunostaining and western blotting evidence showed that phosphorylated tau protein (p-Tau), p-glycogen synthase kinase 3, neurofilament, and apoptosis-related p53, Bcl2-associated X protein, cytochrome c, caspase-9, and caspase-3 were gradually increased, but B-cell lymphoma 2 was gradually decreased with age growth in the cochlea of 3×Tg-AD mice. We suggested that tau hyperphosphorylation and p-Tau 181 aggregation, and mitochondria- and endoplasmic reticulum stress-mediated apoptosis may play a role in the degeneration of SGN in the cochlea. Progressive SGN degeneration in the cochlea may contribute to hearing loss of aging 3×Tg-AD mice.

Original languageEnglish
Pages (from-to)61-71
Number of pages11
JournalChinese Journal of Physiology
Volume64
Issue number2
DOIs
Publication statusPublished - 2021 Mar 1

Keywords

  • Alzheimer's disease
  • apoptosis
  • auditory brainstem response
  • cochlear pathology
  • hearing loss
  • neurofilament
  • spiral ganglion neurons
  • tau hyperphosphorylation
  • transgenic mice

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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