4.5 Article

Changes in calcium-binding protein expression in the auditory brainstem nuclei of the jaundiced Gunn rat

期刊

HEARING RESEARCH
卷 171, 期 1-2, 页码 129-141

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/S0378-5955(02)00494-X

关键词

cochlear nucleus; superior olivary complex; lateral lemniscus nucleus; inferior colliculus; immunohistochemistry; light microscopy; electron microscopy; jaundice; kernicterus; hyperbilirubinemia

资金

  1. NIDCD NIH HHS [R01 DC 00369] Funding Source: Medline

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Sensorineural hearing loss and auditory dysfunction are major sequelae of neonatal hyperbilirubinemia. The sites and cellular effects of bilirubin toxicity in the auditory brainstem pathway are not easily detected. Since altered intracellular calcium homeostasis may play a role in neuronal cell death, we hypothesized that the expression of calcium-binding proteins may be altered in the classic animal model of bilirubin neurotoxicity. The expression of the calcium-binding proteins, calbindin-D28k and parvalbumin, in the brainstem auditory pathway of homozygous recessive jaundiced (jj) Gunn rats was examined by light and electron microscopic immunohistochemistry at 18 days postnatally and compared to the findings obtained from age-matched non-jaundiced heterozygous (Nj) littermate control rats. Immunoreactive staining for both calbindin and parvalbumin was reduced in the cochlear nuclei and the superior olivary complex in jj rats. The extent of the reduction in immunoreactivity was related to the severity of the clinical symptoms. By contrast, immunoreactive staining in other brainstem areas (e.g., dorsal and ventral nuclei of the lateral lemniscus, inferior colliculus), thalamic (medial geniculate body) auditory areas, and neighboring non-auditory structures was similar in jaundiced and control rats. Calbindin-immunoreactive staining in the superior paraolivary and medial superior olivary nuclei in Nj rats was associated with myelinated axons, whereas parvalbumin-immunoreactive staining was localized post synaptically in neuronal somata and dendrites. Immunoreactive staining for the calcium-binding proteins calbindin and parvalbumin in lower brainstem auditory nuclei shows abnormalities in areas susceptible to the effects of hyperbilirubinemia and provides a sensitive new way to assess bilirubin toxicity in the auditory system. (C) 2002 Elsevier Science B.V. All rights reserved.

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