Study Links Missing Protein to Fragile X Patients’ Hypersensitivity to Sound

The fragile X mental retardation protein plays a role in the development of the hearing system, a study in mice reports.

This could explain why people with fragile X syndrome, which is caused by the loss of the FMRP protein, are hypersensitive to sound, researchers said.

In normal circumstances, the FMR1 gene generates FMRP. Its silencing due to a mutation leads to lower levels of the protein, which causes Fragile X syndrome.

People with Fragile X tend to be super-sensitive to sound, showing revved-up responses to sound stimuli.

Studies suggest this is the result of functional and physiological abnormalities in the auditory brainstem, which is part of the central nervous system. The abnormalities cause hearing system dysfunction, scientists believe.

To better understand why Fragile X patients have auditory system abnormalities, a team of researchers investigated the development of sound-processing nerve cells in the auditory system brainstem. This included areas called the ventral cochlear nucleus (VCN), medial nucleus of the trapezoid body (MNTB), and lateral superior olive (LSO).

A key focus of the researchers was whether mice with Fragile X were hypersensitive to sound.

Their study, “Developmental Emergence of Phenotypes in the Auditory Brainstem Nuclei of Fmr1 Knockout Mice,” was published in eNeuro.

The team discovered that Fragile X mouse models of different ages had smaller nerve cells than control mice. They saw the size reduction in various stages of MNTB and LSO nerve cell development, even before the auditory circuits in those brainstem areas were functioning.

Researchers also discovered smaller nerve cells in the VCN area — but not until the mice were able to hear. This suggested that lack of FMRP causes abnormal development of sound-processing nerve cells.

FMRP is produced in brain cells called microglia and astrocytes that can be associated with the nerve cell problems in Fragile X. The research team wondered if microglia in the auditory brainstem could account for hearing dysfunction.

While microglia levels were normal in Fragile X mice, researchers found significantly higher levels of astrocytes in the VCN and LSO areas. This suggested that in addition to affecting the size of nerve cells, FMRP can affect multiple points along the hearing pathway.

Interestingly, while Fragile X is more common in men than women, the researchers discovered that the brain stem did not develop differently in male and female mice with the disorder.

Taken together, the findings indicated that early developmental events can lead to some of the hearing-related abnormalities in Fragile X syndrome.