Cochlear injury and adaptive plasticity of the auditory cortex

Abstract

Growing evidence suggests that cochlear stressors as noise exposure and aging can induce homeostatic/maladaptive changes in the central auditory system from the brainstem to the cortex. Studies centered on such changes have revealed several mechanisms that operate in the context of sensory disruption after insult (noise trauma, drug-, or age-related injury). The oxidative stress is central to current theories of induced sensory-neural hearing loss and aging, and interventions to attenuate the hearing loss are based on antioxidant agent. The present review addresses the recent literature on the alterations in hair cells and spiral ganglion neurons due to noise-induced oxidative stress in the cochlea, as well on the impact of cochlear damage on the auditory cortex neurons. The emerging image emphasizes that noise-induced deafferentation and upward spread of cochlear damage is associated with the altered dendritic architecture of auditory pyramidal neurons. The cortical modifications may be reversed by treatment with antioxidants counteracting the cochlear redox imbalance. These findings open new therapeutic approaches to treat the functional consequences of the cortical reorganization following cochlear damage.

Keywords: auditory cortex; noise-induced hearing loss; oxidative stress; presbycusis; pyramidal neurons.

Figure 1

In the rat, repeated noise exposure causes hearing loss and cochlear oxidative imbalance that is reduced by antioxidant treatment. The diagram in (A) is a schematic representation of the effect of antioxidant supplementation on the upward spread of noise-induced cochlear damage; reactive oxygen species (ROS) over production in cochlear structures induces hair cell dysfunction, spiral ganglion neurons (SGNs) loss and alterations in cortical pyramidal neurons. (A₁) The hearing loss has been evaluated by ABR threshold shift values (±SEM). Repeated noise exposure (100 dB, 10 kHz, 60 min/day for 10 consecutive days) induces threshold shift of ~40–45 dB for all frequencies tested with a peak between 16 and 24 kHz. NIHL is ameliorated by antioxidant treatment (Q_ter, 100 mg/kg × 10 days): the threshold shifts is ~10–15 dB at the end of noise sessions. ***p < 0.0001. (B) The quantitative assessment of HC survival has been determined by Rhodamine–Phalloidin (Rh–Ph) staining of HC apical pole 60 days after noise exposure. In control, typical distribution in three rows of OHCs and one row of inner hair cells (IHCs) is shown [indicated by asterisks in (B₁)], in noise exposed animals HC loss is observed mainly in the middle and basal turn [indicated by asterisks in (B₂)]. The amount of HC disappearance is significantly decreased by antioxidant treatment (B₃). (C) In order to demonstrate that the CoQ analog is protective against oxidative stress in the cochlea, the quantification of quinone levels (CoQ₉) has been performed by HPLC analysis at the end of Q_ter treatment. Interestingly, rats treated with Q_ter show higher quinone levels than in Ctrl and noise groups. The cochlear oxidative damage after noise exposure at day 11 has been detected using superoxide (D) and lipid peroxidation (E) markers. (D) Noise-induced superoxide production in the OHCs [indicated by arrow-heads in (D₂,D₄)] and SGNs (D₃,D₅) is reduced by Q_ter treatment. Similarly, Q_ter treatment significantly decreases the expression of 4-HNE mainly in OHCs [indicated by arrow-heads in (E₂,E₄)] and SGNs (E₃,E₅). Data are taken from Fetoni et al. (2013).

Figure 2

Cortical morphological modifications induced by noise-induced cochlear damage and peripheral deafferentation are ameliorated by antioxidant treatment. (A) Repeated noise exposure induces SGN degeneration, soma appear smaller, their density is reduced, and fibers are thinner (A₁) compared with controls (A). Q_ter administration preserves SGNs and fibers (A₂). (B) The graph shows SGN viability presented as number of cells per square millimeters, ***p < 0.0001. (C–F) Auditory cortex pyramidal neurons belonging to L 2/3 and L 5/6 have been analyzed using Golgi–Cox technique from tissue collected at day 60 after noise exposure. (C) Golgi–Cox staining and Camera Lucida drawings of representative pyramidal neurons belonging to L 2/3 and L 5/6 of auditory cortices. (D–E) Histograms show the effects of noise exposure and antioxidant treatment (Q_ter) on dendritic spine density and length of L 2/3 (above) and L 5/6 (below) pyramidal neurons. Vertical bars indicate SEM, *p < 0.05, **p < 0.001, ***p < 0.0001. (D) The acoustic trauma significantly decreases spine density in the apical and basal dendrites of both cortical layers. Q_ter treatment rescues control values of spine density for both apical and basal dendrites in L 2/3 but not in L 5/6. (E) In both layers, the acoustic trauma significantly increases neuronal length both in apical and basal dendrites. Q_ter treatment does not modify the dendritic length enhanced by the acoustic trauma in the apical and basal arborizations of L 2/3 and L 5/6 pyramidal neurons. (F) Photomicrographs visualize the spines of apical dendritic segments of pyramidal neurons belonging to L 2/3 and L 5/6 of the auditory cortex. Data are adapted from Fetoni et al. (2013).