Hair Cells Essential to Hearing Remain Intact in Older Individuals, but Disconnected from the Brain

Hair cells are the sensors of the ear, picking up vibrations with tiny fibers that give the cells their name. Unfortunately, these cells are not replaced when lost in adult mammals. Loud noise, toxins, and some infectious diseases can cause sufficient loss of hair cells to induce deafness - a condition that currently lacks effective treatments. A sizable fraction of research into the causes of hearing loss has focused on hair cells in the ear, particularly with the growth of the regenerative medicine community. The restoration of lost cell populations is on the horizon, and hair cell regrowth is further advanced than many other lines of work in this field.

Is this approach useful for the types of hearing loss most frequently observed in older individuals, however? The results in today's open access paper can be used to argue that hair cell regrowth may not be sufficient on its own. The authors present evidence for inner hair cells to remain largely intact, while the underlying issue is the death of neurons and their axons connecting these cells to the brain. Reintegration of new hair cells with the complex auditory system of the brain has the look of a much harder problem to solve than the lesser challenge of creating the new hair cells. Rebuilding the connecting axons may not be sufficient on its own, and even that is a hard task to contemplate in comparison to the introduction of new hair cells.

This is one of many examples in which it is an open question as to whether the next generation of regenerative strategies will be sufficient to address specific forms of degeneration that span different organs and tissue types. Will we be fortunate, and find that approaches spurring coordinated localized regrowth do in fact cause reconnection of the nervous system to new tissues and cells? The answer will no doubt be different in each case, and depend on the fine details. The effort must be made, and if it fails, then the more sophisticated efforts of later years will have to be designed, constructed, and take their turn.

Primary Neural Degeneration in the Human Cochlea: Evidence for Hidden Hearing Loss in the Aging Ear

Although sensorineural hearing loss (SNHL) can involve damage to either sensory cells or sensory neurons of the inner ear, a longstanding dogma in acquired SNHL was that loss of sensory cells is the primary event, and that degeneration of auditory nerve fibers (ANFs) occurs only secondarily to the loss of peripheral targets. This view arose because, after cochlear insults such as acoustic injury or ototoxic drugs, the degeneration of sensory cells can be seen within hours post-exposure, whereas degeneration of spiral ganglion cells (SGCs), the cell bodies of the ANFs, is not visible for weeks to months.

Animal work challenged the dogma by showing that hair cell loss in acquired SNHL is neither necessary nor sufficient for loss of ANFs. Firstly, in acoustic injury models, overexposures causing only reversible threshold shifts, and no hair cell loss, can nevertheless cause significant ANF degeneration. The neural damage is visible immediately as loss of synaptic connections between ANFs and inner hair cells (IHCs). In the aging mouse ear, as in the noise-damaged ear, it is the connections between SGCs and IHCs that degenerate first, rather than the hair cells themselves. This primary neural degeneration, or partial de-afferentation of IHCs, has negligible effect on thresholds until it exceeds 80-90%, thus it "hides" behind the audiogram.

The observation that ANF degeneration precedes and/or exceeds hair cell loss in animal models of acquired SNHL has suggested why two people with the same threshold audiogram, whether normal or abnormal, can have very different abilities to understand speech in a noisy environment. i.e. that partial de-afferentation of IHCs, a.k.a. "hidden hearing loss", compromises hearing ability in complex listening environments without changing the ability to detect a pure tone in quiet.

Here we take a direct approach to the question of whether hidden hearing loss is as important in humans as in animal models. We study temporal bones from a group of 20 "normal-aging" humans, ranging in age from birth to 86 years, without any explicit history or ear diseases or ototoxic exposures. We prepare these autopsy specimens in ways that allow us to accurately quantify the survival of hair cells and ANF peripheral axons in the same cochlear regions.

Mean loss of outer hair cells was 30-40% throughout the audiometric frequency range in subjects over 60 yrs, with even greater losses at both apical (low-frequency) and basal (high-frequency) ends. In contrast, mean inner hair cell loss across audiometric frequencies was rarely more than 15%, at any age. Neural loss greatly exceeded inner hair cell loss, with 7 of 11 subjects over 60 years showing more than 60% loss of peripheral axons, and with the age-related slope of axonal loss outstripping the age-related loss of inner hair cells by almost 3:1. The results suggest that a large number of auditory neurons in the aging ear are disconnected from their hair cell targets. This primary neural degeneration would not affect the audiogram, but likely contributes to age-related hearing impairment, especially in noisy environments. Thus, therapies designed to regrow peripheral axons could provide clinically meaningful improvement in the aged ear.

Comments

And the next lap is to suggest not only that hearing loss to a high degree is a neurodegenerative condition but also caused by a chronic inflammation and possibly by senecent cells....

Regardless if the conclusions of this study get confirmed, I don't think repairing and attaching the sensory hairs to the right nerves would be any easier if it was only the hairs that are damaged. You would probably still have to instigate some axon or nerve endings formation. It might be easier to wire a brand new nerve and attach it to the central fibre...

Posted by: Cuberat at August 16th, 2018 8:41 PM

I think an important question to ask is why. Why do these cells not get replaced? Why do they detach? Are there any animals for whom this does not happen? Then why does it not happen for them? What genes are involved? What upstream factors are causing all this to begin with? Does eliminating those factors reverse or at least stop progression?

Posted by: Nathan at August 17th, 2018 1:33 PM

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