Aging after Noise Exposure: Acceleration of Cochlear Synaptopathy in “Recovered” Ears

Abstract

Cochlear synaptic loss, rather than hair cell death, is the earliest sign of damage in both noise-and age-related hearing impairment (Kujawa and Liberman, 2009; Sergeyenko et al., 2013). Here, we compare cochlear aging after two types of noise exposure: one producing permanent synaptic damage without hair cell loss and another producing neither synaptopathy nor hair cell loss. Adult mice were exposed (8 -16 kHz, 100 or 91 dB SPL for 2 h) and then evaluated from 1 h to ϳ20 months after exposure. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses (ABRs). Cochlear whole mounts and plastic sections were studied to quantify hair cells, cochlear neurons, and the synapses connecting them. The synaptopathic noise (100 dB) caused 35-50 dB threshold shifts at 24 h. By 2 weeks, thresholds had recovered, but synaptic counts and ABR amplitudes at high frequencies were reduced by up to ϳ45%. As exposed animals aged, synaptopathy was exacerbated compared with controls and spread to lower frequencies. Proportional ganglion cell losses followed. Threshold shifts first appeared Ͼ1 year after exposure and, by ϳ20 months, were up to 18 dB greater in the synaptopathic noise group. Outer hair cell losses were exacerbated in the same time frame (ϳ10% at 32 kHz). In contrast, the 91 dB exposure, producing transient threshold shift without acute synaptopathy, showed no acceleration of synaptic loss or cochlear dysfunction as animals aged, at least to ϳ1 year after exposure. Therefore, interactions between noise and aging may require an acute synaptopathy, but a single synaptopathic exposure can accelerate cochlear aging.

Complementary metrics of human auditory nerve function derived from compound action potentials

“…Growing evidence from animal and human studies suggests that a loss or dysfunction of 342 AN fibers, particularly those with low-SRs, contributes to suprathreshold auditory processing 343 deficits (Kujawa and Liberman 2009;Liberman et al 2015;Schmiedt et al 1996). The 344 goal of the current experiment was to develop and validate new metrics from the CAP to better 345 characterize AN function in humans and reveal the contributions of neural synchrony and slower 346 AN, such as those with low-SR fibers.…”

“…http://dx.doi.org/10.1101/213157 doi: bioRxiv preprint first posted online contribution of AN fibers to the CAP; increasing doses of ouabain were delivered to the roundchanges in Wave I of the ABR, including increased thresholds and decreased response 378 amplitudes (Fernandez et al 2015;Lang et al 2010;Mehraei et al 2016;Sergeyenko et al 379 2013). The contribution of low-SR fibers to the CAP has also been demonstrated in the 380 recovery of the CAP response from prior stimulation, both in animals where the distribution of 381 low-SR fibers was estimated (Schmiedt et al 1996), and in humans (Murnane et al 1998).…”

“…In animals, cochlear synaptopathy and deficits in AN function can be identified via the 390 suprathreshold amplitudes of the CAP response or wave I of the auditory brainstem response 391 (ABR) (Fernandez et al 2015;Sergeyenko et al 2013). In humans, the use of CAP amplitudes 392 as a marker of AN integrity is complicated by factors unrelated to AN integrity, including 393 electrode location and resistance, head size, etc.…”

Pathological Changes in the Inner Ear in Experimental Modeling of Sensorineural Hearing Loss in Animals

“…Безусловно, в отечественной науке предстоит восполнить этот пробел, и особое место при этом принадлежит экспериментальным исследовани-ям с изучением слуховых структур на клеточном уровне. Остается дискутабельным и вопрос о при-оритетной гибели наружных волосковых клеток (НВК) или нейронов спирального ганглия при СНТ [7], о выраженности некротических и апоптических проявлений клеточной гибели при повреждениях внутреннего уха [8,9,10]. Не исключено, что пре-обладание определённых нарушений связано с различающимися параметрами и длительностью воздействия раздражителя, что требует дополни-тельно экспериментальной оценки значения этих факторов.…”

A Life Course Approach to Hearing Health

“…We do not know to what degree recognized risk factors for hearing loss in the prenatal and early childhood periods continue to act as risk factors for hearing loss in later childhood, adolescence, and throughout adult life. What is more, there is evidence from animal studies to suggest that an early history of noise exposure can impact auditory function later in life (Fernandez et al 2015). However, there is little longitudinal data to help determine whether hearing loss in middle and old age is preceded by threshold shifts earlier in life nor whether deteriorations in hearing ability in this middle phase of life occur continuously, or in a stepwise fashion.…”