Abstract

Conductive hearing loss causes a progressive decline in cochlear activity that may result in functional and structural modifications in auditory neurons. However, whether these activity-dependent changes are accompanied by a glial response involving microglia, astrocytes, or both has not yet been fully elucidated. Accordingly, the present study was designed to determine the involvement of glial related mechanisms in the anteroventral cochlear nucleus (AVCN) of adult rats at 1, 4, 7, and 15 d after removing middle ear ossicles. Quantitative immunohistochemistry analyses at light microscopy with specific markers of microglia or astroglia along with immunocytochemistry at the electron microscopy level were used. Also, in order to test whether trophic support by neurotrophins is modulated in glial cells by auditory activity, the expression and distribution of neurotrophin-3 (NT-3) and its colocalization with microglial or astroglial markers was investigated. Diminished cochlear activity after middle ear ossicle removal leads to a significant ipsilateral increase in the mean gray levels and stained area of microglial cells but not astrocytes in the AVCN at 1 and 4 d post-lesion as compared to the contralateral side and control animals. These results suggest that microglial cells but not astrocytes may act as dynamic modulators of synaptic transmission in the cochlear nucleus immediately following unilateral hearing loss. On the other hand, NT-3 immunostaining was localized mainly in neuronal cell bodies and axons and was upregulated at 1, 4 and 7 d post-lesion. Very few glial cells expressed this neurotrophin in both control and experimental rats, suggesting that NT-3 is primarily activated in neurons and not as much in glia after limiting auditory activity in the AVCN by conductive hearing loss.

Highlights

  • Conductive hearing loss is a condition that results in diminished cochlear nerve synaptic activity due to an inefficient sound transmission from the middle to the inner ear (Conlee and Parks, 1981; Tucci and Rubel, 1985)

  • AUDITORY BRAINSTEM RESPONSES (ABR) To evaluate alterations in auditory function following unilateral conductive hearing loss (UCHL), ABR recordings were performed in rats before and after unilateral ossicle removal for each of the time points described in the Materials and Methods Section

  • The present study demonstrates that UCHL, which causes a progressive decline in cochlear nerve activity, leads initially to an increase in microglial but not astroglial activation in the anteroventral cochlear nucleus (AVCN) of adult rats, at least up to 15d after the lesion

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Summary

Introduction

Conductive hearing loss is a condition that results in diminished cochlear nerve synaptic activity due to an inefficient sound transmission from the middle to the inner ear (Conlee and Parks, 1981; Tucci and Rubel, 1985). In an attempt to improve the diagnosis and treatment of these patients, animal models of conductive hearing loss have been developed to elucidate the morphological and functional anomalies associated with these pathological responses In this regard, a series of studies have demonstrated that unilateral restriction of peripheral inputs to central auditory nuclei leads to decreased activity in auditory neurons of the affected side (Tucci et al, 1999, 2001, 2002; Hutson et al, 2007), strengthening of the ipsilateral projection from the cochlear nucleus to inferior colliculus (Moore et al, 1989), alterations in neurotransmitters release and uptake (Potashner et al, 1997; Suneja et al, 1998), redistribution of AMPA and glycine receptor subunits (Whiting et al, 2009), and modifications in the synthesis and composition of glutamate and glycine receptors (Wang et al, 2011)

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