Elsevier

Hearing Research

Volume 233, Issues 1–2, November 2007, Pages 124-134
Hearing Research

Research paper
Consequences of unilateral hearing loss: Time dependent regulation of protein synthesis in auditory brainstem nuclei

https://doi.org/10.1016/j.heares.2007.08.003Get rights and content

Abstract

Conductive hearing impairment results in marked changes in neuronal activity in the central auditory system, particularly in young animals [Tucci, D.L., Cant, N.B., Durham, D., 1999. Conductive hearing loss results in a decrease in central auditory system activity in the young gerbil. Laryngoscope 109, 1359–1371]. To better understand the effects of conductive hearing loss (CHL) on cellular metabolism, incorporation of 3H-leucine was used as a measure of protein synthesis in immature postnatal day 21 gerbils subjected to either unilateral CHL by malleus removal or profound sensorineural hearing loss by cochlear ablation. 3H-leucine uptake was measured after survival times of 6 or 48 h. Protein synthesis values were standardized to measurements from the abducens nucleus and compared with measurements from sham animals at similar age/survival times. Protein synthesis in the medial superior olive (MSO) was found to be significantly down-regulated (bilaterally) after CHL in animals surviving 48 h. However, 6 h after CHL manipulation, protein synthesis is up-regulated in MSO (bilaterally) and in the ipsilateral medial nucleus of the trapezoid body.

Introduction

Conductive hearing loss (CHL) changes the way sound is processed in the central auditory system. Using 2-deoxyglucose (2-DG) as a measure of neuronal activity, unilateral CHL has been shown to produce changes in glucose uptake, with significantly reduced uptake in the major afferent projection originating from the affected ear (Tucci et al., 1999). Effects are most marked in young, developing animals. In these animals, CHL results in a decrease that is statistically similar to that observed following cochlear ablation (CA), despite the more substantial (profound) hearing loss observed after the latter manipulation.

Cochlear destruction causes transneuronal degeneration in central auditory pathways (e.g., Jean-Baptiste and Morest, 1975, Pasic et al., 1994, Morest and Bohne, 1997, Potashner et al., 1997, Tierney et al., 1997). Furthermore, studies of CA-induced plasticity within these pathways have shown that CA affects the internal metabolism of central auditory system neurons. For example, the regulation of glutamate and glycine release by protein kinase is altered by CA (Zhang et al., 2002, Zhang et al., 2003a, Zhang et al., 2003b, Zhang et al., 2004), as are signal transduction pathways (Suneja and Postashner, 2003) and cyclic AMP levels (Mo et al., 2006). CA also can induce the re-emergence of GAP-43 expression in adult animals (Illing et al., 1997, Michler and Illing, 2002, Kraus and Illing, 2004). Each of these findings suggests that CA may have an affect on central auditory system neurons at the gene level (Holt et al., 2005).

Cellular changes following CHL are less dramatic (Webster and Webster, 1979, Webster, 1983a, Webster, 1983b, Webster, 1983c, Coleman and O’Connor, 1979, Blatchley et al., 1983, Trune and Morgan, 1988a, Trune and Morgan, 1988, Doyle and Webster, 1991, Walsh and Webster, 1994, Tucci and Rubel, 1985, Tucci et al., 1987, Moore et al., 1989), but there is evidence that the auditory deprivation produced by CHL, particularly if unilateral, alters the way that sound is processed, at least in lower brainstem nuclei. Some authors suggest that the symmetry of input may be important in establishing and maintaining neural projections, and that unilateral CHL may alter the anatomical structure of bilaterally innervated nuclei (Killackey and Ryugo, 1977). Moore et al. (1989) found that, despite the lack of change in neuron area in ipsilateral CN following unilateral CHL, there was a significant change in the projection from the CN opposite the affected ear to the ipsilateral IC, reflecting a possible compensatory increase in input to the IC from the normal ear (uncrossed pathway). In the barn owl, Knudsen (1999) found evidence for altered localization cues and reorganization of binaurally innervated central auditory nuclei following unilateral CHL produced by occlusive earplug placement during a critical period in development.

2-DG uptake is decreased in the ipsilateral cochlear nucleus after unilateral CHL, and there is information from several studies indicating there may be up-regulation of the contralateral cochlear nucleus (Tucci et al., 1999). Following unilateral CHL in young adult (6 week old) gerbils, there is a slight but significant increase in 2-DG uptake in the contralateral cochlear nucleus that is not seen following cochlear ablation (Tucci et al., 1999). A similar pattern of change, although less marked, is observed in cytochrome oxidase (CO) activity following unilateral CHL (Tucci et al., 2001). In this experiment, for adult animals, a significant decrease in CO activity is observed in the ipsilateral and a significant increase is observed in the contralateral anteroventral cochlear nucleus (AVCN). Morphological changes have also been observed in the contralateral AVCN after unilateral hearing loss, where a slight increase in the size of spherical cells has been reported (e.g., Coleman and O’Connor, 1979, Dodson et al., 1994).

Possible compensatory changes were also observed in the contralateral AVCN following CHL in adult guinea pigs (Sumner et al., 2005). In that study of binaural properties of AVCN neurons following unilateral conductive impairment, the investigators found a dramatic increase in the proportion of units in the ipsilateral AVCN that responded with excitation to broad band noise stimulation of the contralateral (intact) ear.

One consequence of severe end organ damage on cellular metabolism is a decrease in protein synthesis in the ipsilateral cochlear nucleus (Steward and Rubel, 1985, Born and Rubel, 1988, Hyson and Rubel, 1989, Sie and Rubel, 1992). A similar decrease in protein synthesis has also been observed in the ipsilateral cochlear nucleus following unilateral CHL (Trune and Kiessling, 1988). However, little is known about how unilateral hearing loss affects protein synthesis in other auditory brainstem structures. In order to better understand some of the cellular events associated with changes in central auditory system activity subsequent to CHL, we initiated the current study to investigate protein synthesis in central auditory system nuclei in immature gerbils.

Section snippets

Subjects

Thirty-three Mongolian gerbils (Meriones unguiculatus) obtained from a commercial supplier (Charles River) were used in the present study. All anesthetic, operative, and postoperative procedures and care were approved by the Institutional Animal Care and Use Committee and followed NIH guidelines. All animals entered the experimental paradigm at postnatal day 21 (P21).

Protein synthesis was examined in animals subsequent to a sham (SH), CHL, or CA procedure, with survival times of 6 h (SH = 5, CHL = 

Results

We used cellular incorporation of 3H-leucine as a tool to measure the relative level of protein synthesis in central auditory system structures subsequent to a unilateral hearing loss induced by middle or inner ear manipulation. The incorporation of amino acid was measured over a brief 30-minute “window” immediately preceding euthanasia. We found no significant left–right differences among SH animals of a particular age group. Therefore, left and right SH data for each structure were combined

Discussion

Cellular incorporation of 3H-leucine was used as a measure of protein synthesis in animals with an abrupt unilateral hearing loss induced at P21. We found significant differences in leucine uptake in AVCN and MTB after 6 h, in MSO after 6 and 48 h. The results of this study demonstrate that hearing loss, whether conductive or sensorineural, alters protein synthesis in central auditory system structures.

Acknowledgements

The authors would like to thank Jason Maloney and Adam Graff for their technical contributions during the tissue analysis phase of this report. Grant Sponsor: National Institute of Health/National Institute on Deafness and Other Communication Disorders; Grant Number: DC05416 to DLT.

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