Examination of calcium-binding protein expression in the inner ear of wild-type, heterozygous and homozygous pituitary adenylate cyclase-activating polypeptide (PACAP)-knockout mice in kanamycin-induced ototoxicity

A. Nemeth, K. Szabadfi, B. Fulop, D. Reglodi, P. Kiss, J. Farkas, B. Szalontai, R. Gabriel, H. Hashimoto, A. Tamas

Research output: Article

9 Citations (Scopus)

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with diverse biological effects. It also occurs and exerts protective effects in sensory organs; however, little is known about its effects in the auditory system. Recently, we have shown that PACAP protects cochlear cells against oxidative-stress-induced apoptosis and homozygous PACAP-deficient animals show stronger expression of Ca2+-binding proteins in the hair cells of the inner ear, but there are no data about the consequences of the lack of endogenous PACAP in different ototoxic insults such as aminoglycoside-induced toxicity. In this study, we examined the effect of kanamycin treatment on Ca2+-binding protein expression in hair cells of wild-type, heterozygous and homozygous PACAP-deficient mice. We treated 5-day-old mice with kanamycin, and 2 days later, we examined the Ca 2+-binding protein expression of the hair cells with immunohistochemistry. We found stronger expression of Ca2+-binding proteins in the hair cells of control heterozygous and homozygous PACAP-deficient mice compared with wild-type animals. Kanamycin induced a significant increase in Ca2+-binding protein expression in wild-type and heterozygous PACAP-deficient mice, but the baseline higher expression in homozygous PACAP-deficient mice did not show further changes after the treatment. Elevated endolymphatic Ca2+ is deleterious for the cochlear function, against which the high concentration of Ca 2+-buffers in hair cells may protect. Meanwhile, the increased immunoreactivity of Ca2+-binding proteins in the absence of PACAP provide further evidence for the important protective role of PACAP in ototoxicity, but further investigations are necessary to examine the exact role of endogenous PACAP in ototoxic insults.

Original languageEnglish
Pages (from-to)57-67
Number of pages11
JournalNeurotoxicity Research
Volume25
Issue number1
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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