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Glutamate is the afferent neurotransmitter in the human cochlea
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. (Oto-Rhino-Laryngology, Head & Neck Surgery)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
2000 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 120, no 3, 359-362 p.Article in journal (Refereed) Published
Abstract [en]

Glutamate, the most important afferent neurotransmitter in the auditory system, is thought to be the afferent transmitter between the cochlear inner hair cells and afferent neurons, hitherto visualized only in the cochlea of animal species. It has been identified for the first time in sections from the human inner ear. L-glutamate, NMDAR2B and the enzyme glutamine synthetase were identified by using monoclonal antibodies. The distribution pattern of the transmitter L-glutamate in the human cochlea is similar to that observed in other mammals. L-glutamate was identified adjacent to outer and inner hair cells and in the spiral ganglion. Similar distributions were found for glutamine synthetase and the ionotropic NMDA receptor subunit NMDAR2. The identification of neurotransmitters and their receptors in the human cochlea has implications for the pharmacotherapy of inner ear diseases.

Place, publisher, year, edition, pages
2000. Vol. 120, no 3, 359-362 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-89798PubMedID: 10894409OAI: oai:DiVA.org:uu-89798DiVA: diva2:161562
Available from: 2002-04-10 Created: 2002-04-10 Last updated: 2017-12-14Bibliographically approved
In thesis
1. The Round Window Membrane - Gateway to the Cochlea: A Morphological and Electrophysiological study
Open this publication in new window or tab >>The Round Window Membrane - Gateway to the Cochlea: A Morphological and Electrophysiological study
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Topical treatment of several inner ear diseases through the round window membrane (RWM) might be feasible in the near future. Bacteria toxins, ototoxic drugs and noise trauma seem to harm the inner ear by a common pathway which involves, excessive outflow of the afferent neurotransmitter glutamate and formation of nitric oxide (NO), which can severely damage cells/nerve endings and lead to cell death.

In this study we used 98 Sprague-Dawley rats and seven human temporal bones. Various substances were instilled into the middle ear of the rat, such as Pseudomonas Aeruginosa Exotoxin (PaExoA), gentamicin, NO-inhibitor N-Omega-Nitro-L-Arginine Methyl Ester (L-NAME), and glucocorticoids. The effects of the substances were studied by morphological analysis of RWM and the endolymphatic sac (ES) by light and electron microscopic. Hearing level was measured in the rats by ABR technique. The human temporal bones were studied immunomorphologically to search for glutamate.

In the human inner ear, glutamate receptors and glutamine synthetase, were identified. In the rat, we found, following PaExoA exposure, reversible and permanent hearing loss and morphological changes in the RWM. The ES showed increased numbers of macrophages and thickening of the epithelia. When L-NAME was used as an otoprotector from gentamicin ototoxicity a therapeutic effect in the high frequency area was found. Hydrocortisone (but not dexamethasone) exposure of the RWM resulted in membrane thickening, and adjacent to the membrane, inflammatory cells.

The importance of the RWM as a portal for toxic substances and topical treatment of inner ear diseases was highlighted in this study. The difficulties of applying drugs in the round window niche were exposed. The results of this study add important knowledge concerning certain mechanisms of inner ear injury and help us to understand possibilities and problems of local treatment of inner ear diseases in patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 33 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1134
Keyword
Otorhinolaryngology, round window membrane, pseudomonas exotoxin, auditory brainstem response, hearing loss, endolymphatic sac, inner ear immunology, glutamate, nitric oxide inhibitor, glucocorticoid., Otorhinolaryngologi
National Category
Otorhinolaryngology
Research subject
Oto-Rhino-Laryngology
Identifiers
urn:nbn:se:uu:diva-1969 (URN)91-554-5277-9 (ISBN)
Public defence
2002-05-03, Skoogsalen, ingång 78/79, 1 trappa, Uppsala, 13:15
Opponent
Available from: 2002-04-10 Created: 2002-04-10Bibliographically approved

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Nordang, LeifAnniko, Matti

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