BioTechniques
11/03/2014 Jeffrey M. Perkel, PhD
Hearing loss due to "acoustic trauma"—such as that experienced at a rock concert—stems in part from a loss of synaptic connections in the ear. Now researchers have discovered a neural growth factor that can promote recovery from that damage, at least in mice.
Gabriel Corfas, Professor in the Department of Otolaryngology and Head and Neck Surgery at the University of Michigan, and his team report in the journal eLife that the neurotrophic factor Ntf3, produced by glia-like “supporting cells,” promotes synapse formation (and thus hearing) in the cochlea after birth. And Ntf3 overexpression following traumatic hearing loss led to improved recovery of synaptic density and hearing, suggesting a potential therapeutic strategy—assuming these results can be extended to humans.
Ntf3 is required for neuronal survival and development during embryogenesis, but it continues to be expressed in the ear after birth. To understand why, Corfas and his team created mouse strains in which they either deleted or overexpressed Ntf3 in specific cell populations postnatally.
Targeted deletion of Ntf3 from supporting cells caused a decrease in synapse density in the cochlea and elevated auditory thresholds—that is, fewer neuronal connections and concomitant hearing loss. Conversely, overexpressing Ntf3 lead to increased synapse formation and a heightened sense of hearing.
These results implicated Ntf3 in wiring the neuronal circuitry of the ear and raised the question of whether this information could be exploited for therapeutic purposes.
When an animal is exposed to loud noise for extended periods, it will have trouble hearing afterwards. This temporary hearing loss disappears within a few days, but synaptic connections are nonetheless lost.
To find out if Ntf3 could mitigate that impact, the authors exposed three groups of mice to acoustic trauma—the laboratory equivalent of attending a rock concert. One group was a control; the second group overexpressed Ntf3 prior to the trauma; and a third overexpressed Ntf3 immediately afterwards. The team then measured hearing and synapse numbers up to two weeks later.
Ntf3 cannot prevent synapse loss, the results indicated. But overexpression does promote improved recovery of hearing and synapse density compared to controls—albeit not to wild-type levels.
“Animals that have extra Ntf3 recover, regenerate, and reform synapses, and therefore they recover better function than those mice that do not have it,” Corfas said.
Now, Corfas and his team are digging deeper into questions such as how long after auditory insult Ntf3 overexpression is useful; if it is possible to achieve higher levels of synapse recovery; and if this approach can be applied to age-related hearing loss as well. Once those questions are answered, the team can turn its attention to hearing loss in humans.
Reference
G. Wan, et al., “Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma,” eLife, 10.7554/eLife.03564, 2014.
11/03/2014 Jeffrey M. Perkel, PhD
Hearing loss due to "acoustic trauma"—such as that experienced at a rock concert—stems in part from a loss of synaptic connections in the ear. Now researchers have discovered a neural growth factor that can promote recovery from that damage, at least in mice.
Gabriel Corfas, Professor in the Department of Otolaryngology and Head and Neck Surgery at the University of Michigan, and his team report in the journal eLife that the neurotrophic factor Ntf3, produced by glia-like “supporting cells,” promotes synapse formation (and thus hearing) in the cochlea after birth. And Ntf3 overexpression following traumatic hearing loss led to improved recovery of synaptic density and hearing, suggesting a potential therapeutic strategy—assuming these results can be extended to humans.
Ntf3 is required for neuronal survival and development during embryogenesis, but it continues to be expressed in the ear after birth. To understand why, Corfas and his team created mouse strains in which they either deleted or overexpressed Ntf3 in specific cell populations postnatally.
Targeted deletion of Ntf3 from supporting cells caused a decrease in synapse density in the cochlea and elevated auditory thresholds—that is, fewer neuronal connections and concomitant hearing loss. Conversely, overexpressing Ntf3 lead to increased synapse formation and a heightened sense of hearing.
These results implicated Ntf3 in wiring the neuronal circuitry of the ear and raised the question of whether this information could be exploited for therapeutic purposes.
When an animal is exposed to loud noise for extended periods, it will have trouble hearing afterwards. This temporary hearing loss disappears within a few days, but synaptic connections are nonetheless lost.
To find out if Ntf3 could mitigate that impact, the authors exposed three groups of mice to acoustic trauma—the laboratory equivalent of attending a rock concert. One group was a control; the second group overexpressed Ntf3 prior to the trauma; and a third overexpressed Ntf3 immediately afterwards. The team then measured hearing and synapse numbers up to two weeks later.
Ntf3 cannot prevent synapse loss, the results indicated. But overexpression does promote improved recovery of hearing and synapse density compared to controls—albeit not to wild-type levels.
“Animals that have extra Ntf3 recover, regenerate, and reform synapses, and therefore they recover better function than those mice that do not have it,” Corfas said.
Now, Corfas and his team are digging deeper into questions such as how long after auditory insult Ntf3 overexpression is useful; if it is possible to achieve higher levels of synapse recovery; and if this approach can be applied to age-related hearing loss as well. Once those questions are answered, the team can turn its attention to hearing loss in humans.
Reference
G. Wan, et al., “Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma,” eLife, 10.7554/eLife.03564, 2014.