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Ototoxicity-related changes in GABA immunolabeling within the rat inferior colliculus.
Holt, Avril Genene; Griffith, Ronald D; Lee, Soo D; Asako, Mikiya; Buras, Eric; Yalcinoglu, Selin; Altschuler, Richard A.
Afiliação
  • Holt AG; Ophthalmology, Visual and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, United States of America. Electronic address: agholt@med.wayne.edu.
  • Griffith RD; Ophthalmology, Visual and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, United States of America.
  • Lee SD; Kresge Hearing Research Institute, Department of Otolaryngology, Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, United States of America.
  • Asako M; Department of Otolaryngology, Kansai Medical University, Takii Hospital, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan.
  • Buras E; Kresge Hearing Research Institute, Department of Otolaryngology, Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, United States of America.
  • Yalcinoglu S; Ophthalmology, Visual and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, United States of America.
  • Altschuler RA; Kresge Hearing Research Institute, Department of Otolaryngology, Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, United States of America; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, United States of America.
Hear Res ; 452: 109106, 2024 10.
Article em En | MEDLINE | ID: mdl-39181061
ABSTRACT
Several studies suggest that hearing loss results in changes in the balance between inhibition and excitation in the inferior colliculus (IC). The IC is an integral nucleus within the auditory brainstem. The majority of ascending pathways from the lateral lemniscus (LL), superior olivary complex (SOC), and cochlear nucleus (CN) synapse in the IC before projecting to the thalamus and cortex. Many of these ascending projections provide inhibitory innervation to neurons within the IC. However, the nature and the distribution of this inhibitory input have only been partially elucidated in the rat. The inhibitory neurotransmitter, gamma aminobutyric acid (GABA), from the ventral nucleus of the lateral lemniscus (VNLL), provides the primary inhibitory input to the IC of the rat with GABA from other lemniscal and SOC nuclei providing lesser, but prominent innervation. There is evidence that hearing related conditions can result in dysfunction of IC neurons. These changes may be mediated in part by changes in GABA inputs to IC neurons. We have previously used gene micro-arrays in a study of deafness-related changes in gene expression in the IC and found significant changes in GAD as well as the GABA transporters and GABA receptors (Holt 2005). This is consistent with reports of age and trauma related changes in GABA (Bledsoe et al., 1995; Mossop et al., 2000; Salvi et al., 2000). Ototoxic lesions of the cochlea produced a permanent threshold shift. The number, intensity, and density of GABA positive axon terminals in the IC were compared in normal hearing and deafened rats. While the number of GABA immunolabeled puncta was only minimally different between groups, the intensity of labeling was significantly reduced. The ultrastructural localization and distribution of labeling was also examined. In deafened animals, the number of immuno gold particles was reduced by 78 % in axodendritic and 82 % in axosomatic GABAergic puncta. The affected puncta were primarily associated with small IC neurons. These results suggest that reduced inhibition to IC neurons contribute to the increased neuronal excitability observed in the IC following noise or drug induced hearing loss. Whether these deafness diminished inhibitory inputs originate from intrinsic or extrinsic CNIC sources awaits further study.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colículos Inferiores / Ratos Sprague-Dawley / Ácido gama-Aminobutírico Limite: Animals Idioma: En Revista: Hear Res Ano de publicação: 2024 Tipo de documento: Article País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colículos Inferiores / Ratos Sprague-Dawley / Ácido gama-Aminobutírico Limite: Animals Idioma: En Revista: Hear Res Ano de publicação: 2024 Tipo de documento: Article País de publicação: Holanda