Early Sound Exposure May Prevent Hypersensitivity to Noise in Fragile X, Mouse Study Suggests

Exposure to sound at an early age may prevent brain changes related to sound hypersensitivity in people with fragile X syndrome, a study in a mouse model suggests. 

The study, “Beneficial effects of sound exposure on auditory cortex development in a mouse model of Fragile X Syndrome,” was published in the journal Neurobiology of Disease. 

People with fragile X, the leading genetic cause of autism, are hypersensitive to sounds, which may lead to seizures. This abnormal sensitivity is caused by the altered development of nerve cells in the area of the brain that responds to sound, called the auditory cortex.   

Sound hypersensitivity also occurs in people with autistic spectrum disorder (ASD) — an umbrella term used for deficits in social communication and restricted, repetitive patterns of behavior and interests. In children with ASD, muffling sound with earmuffs and noise-cancelling headphones has been beneficial in controlling behavior problems related to exaggerated reactivity to sound.

Researchers at University of California, Riverside explored whether a similar strategy at an early age may ease or prevent the development of sound hypersensitivity in fragile X. They used mice lacking the Fmr1 gene — the gene that causes fragile X when mutated — which also experience sound hypersensitivity.

These mice, along with control animals, were housed with their mothers in a soundproof box days after birth. From nine to 21 days after birth, they were exposed to continuous regular sound pips at a single high-pitched tone. 

To assess the effects of muffling sound, a separate group of mice were put in a sound reduction chamber that prevented tone exposure.

All mice underwent a brainwave pattern analysis that measured specific signals known to be altered in people with fragile X, called auditory event-related potentials (ERPs).

Contrary to what the researchers expected, results showed that sound reduction actually further aggravated the abnormal ERP patterns compared with control mice. Likewise, mice with fragile X exposed to sound reduction also showed increased density of immature nerve cell protrusions known as dendritic spines, as seen in people with fragile X. Of note, dendritic spines are crucial in synapses, the site where nerve cells communicate.

In contrast, sound exposure normalized ERPs and the density of dendritic spines in the mouse model. It also corrected the delayed development of auditory cortex neurons that produce the protein parvalbumin, as well as cells that wrap around and regulate the activation of parvalbumin cells, called perineuronal nets.

“These beneficial effects of sound exposure were a surprise because we expected a sound reduction would prevent hyperresponsiveness and reduce … sensitivity to sound,” Iryna Ethell, PhD, the study’s senior author, said in a press release. “Perhaps exposure to sounds, rather than isolation, in early development of individuals living with [fragile X] is a better approach to treat hypersensitivity.”

Yet, the team wrote that “more studies are necessary to investigate which parameters of the sound exposure are key to observed changes and to understand long-lasting effects of the early developmental exposure.”