Tuesday , March 2 2021

Early exposure to sounds may address noise hypersensitivity associated with Fragile X Syndrome – ScienceDaily

A research team at the University of California at Riverside found exposure to sound – not sound reduction – during the early development of mice designed to have Fragile X Syndrome, or FXS, restores molecular, cellular and functional properties in the auditory cortex. , the area of ​​the brain that processes sounds.

The results suggest that facilitating exposure to sounds during young age may restore communication between brain cells that have been altered by the genetic mutation that leads to FXS.

Caused by genetic abnormalities, FXS, the most common inherited cause of intellectual disability and autism, affects approximately 1 in 4,000 men and 1 in 6,000 women. About 1 in 259 women carry FXS and can pass it on to their children. Children, especially boys, with FXS have neurodevelopmental and neuropsychiatric disabilities, including hyperactivity.

Humans with FXS and other autism spectrum disorders, or ASDs, are hypersensitive to sounds. In fact, it is not uncommon to see people living with FXS or ASDs often close their ears or wear sound-canceling headphones. Some loud sounds can even lead to seizures in these individuals.

"Our study found that raising FXS mice in a sound-limiting environment leads to even more severe abnormalities than FXS mice raised in a noisy nursery," said Iryna Ethell, professor of biomedical sciences at the School of Medicine, who led the study. search.

The researchers examined structural changes in the auditory cortex of FXS mice at the cellular level and found that sound reduction – or attenuation – leads to a loss of inhibitory neurons in the brain. Loss of these neurons, which reduce brain activity, is probably responsible for hypersensitivity in FXS. Exposure to sound, on the other hand, restores the levels of these neurons and brain responses to the normal range.

"Perhaps exposure to sounds rather than isolation in the early development of individuals living with FXS is a better approach to treating hypersensitivity," Ethell said.

The study, published in Disease Neurobiology, is the first to show the beneficial effects of pure tone developmental exposure in an FXS mouse model.

"Our findings provide a scientific basis for future clinical work using sound exposure as therapy in addition to medications," Ethell said. "Sensitivity in individuals with FXS and ASDs is not limited to sound. Other sensory modalities have similar preventive effects – such as light, touch and smell. Our findings, therefore, may have broader implications for multisensory exposure."

In one experiment, the researchers placed FXS mice in a sound-limiting box five days after birth. They then examined their responses to reduced sound using electrophysiology. They also measured anatomical and biochemical changes in the brain when mice were 21 days old. In another experiment, the researchers placed different FXS mice in a similar box five days after birth, but exposed them to loud sounds. They then performed a similar analysis on these mice when they were 21 days old.

The researchers unexpectedly found that exposure of FXS mice to repeated presentations of a 14 kilohertz tone at a 5 hertz repetition rate for 24 hours a day, from when mice were 9 days to 21 days normalized their responses to sound and corrected deficits observed in FXS rats.

"These beneficial effects of sound exposure came as a surprise because we hoped a reduction in sound would prevent hyperresponsiveness and reduce the sensitivity of FXS mice to sound," Ethell said.

Ethell's lab study, conducted in collaboration with the labs of Khaleel Razak, professor of psychology; and Devin Binder, a professor of biomedical science, was supported by a three-year Department of Defense grant.

Laboratories will then identify specific beneficial properties of sound and examine whether it is useful to combine sound exposure with a pharmacological approach.

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