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Scientists Find Hearing Loss Connection In Autism Spectrum Study

Previous studies of aging-related hearing loss showed that the brain can increase its response to make up for reduced auditory signals from the inner ear.

World Autism Day
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Scientists have discovered hearing impairment in a preclinical model of autism spectrum disorder (ASD), according to a new study. The researchers observed mild hearing loss and defects in auditory nerve function. Closer examination of the nerve tissue revealed abnormal supportive cells called glia, aging-like degeneration, and inflammation, it said.
Many patients with ASD show increased sensitivity to sound. While many scientists in the past have looked to the brain for an underlying cause, the team at the Medical University of South Carolina (MUSC), the US, took a different approach by studying the peripheral hearing system.
The findings from this study, published in the Journal of Neuroscience, highlight the importance of considering sensory organs and their interactions with the brain in understanding ASD, said the study.
"Hearing impairment may have an impact on the higher-level auditory system and, eventually, cognitive function," said Hainan Lang, senior author of the study.
Previous studies of aging-related hearing loss showed that the brain can increase its response to make up for reduced auditory signals from the inner ear. Lang wanted to find out if this increase, called central gain, could contribute to abnormal brain response to sound in ASD. However, a significant obstacle lay in her path.
"We didn't have a clinically relevant model to directly test this important fundamental question," said Lang.
The preclinical model that would allow Lang to test her hypothesis was developed in the lab of Christopher Cowan, Ph.D., chair of Neuroscience at MUSC. Mice in this model have only one working copy of a gene called MEF2C.
Cowan's group had studied MEF2C in the past for its role in brain development and found that it was important for regulating circuit formation in the brain. They became especially interested in creating a preclinical model when a group of patients with ASD-like symptoms were identified with MEF2C mutations.
Cowan's models also show ASD-like behaviours, including increased activity, repetitive behavior, and communication deficits.
Lang and team first measured the response of the brain to auditory signals, using a modified version of a test that is commonly used to screen newborn infants for hearing loss. Mild hearing loss was observed in the mice with only one working copy of MEF2C while hearing remained normal in those with two working copies.
To investigate this loss further, the researchers measured the activity of the auditory nerve, which carries signals from the inner ear to the brain. They found reduced activity in this nerve in mice with only one copy of MEF2C.
With their sights set on the auditory nerve, the researchers used advanced microscopes and staining techniques to determine what was going wrong. Although the overall hearing sensitivity loss was mild, the researchers were excited to see a big difference in auditory nerve response. Nerves from mice with a single copy of MEF2C showed cellular degeneration much like that seen in age-related hearing loss.
The researchers also saw signs of increased inflammation, with disrupted blood vessels and activated immune cells called glia and macrophages. This finding was especially surprising to the researchers.
 "Glial cells were not my first thought; I thought it was a neuronal change," said Lang.
 "Now we understand that auditory nerve activity can also involve the immune system, and that's the beautiful new direction we want to continue to study," said Lang.
Cowan also believes that the finding opens the way for a new area of neuroscience research.
"We have more appreciation now that there is an important interaction between the immune system in your body and the immune system in your brain," he said.
"The two systems play critical roles in shaping how nervous system cells communicate with each other, in part, by pruning excess or inappropriate connections that have formed, and this is an essential aspect of healthy brain development and function," said Cowan.
The findings from this study could be important not only for patients who are MEF2C deficient but also for people with ASD or hearing loss as a whole.
"Understanding how this gene may be participating in ear development and how the inner ear development is affecting brain development has tremendous applicability," said Cowan.
In future studies, the researchers aim to discover how exactly MEF2C causes the changes that were identified in this study. The research team also hopes to explore these findings in patients with MEF2C deficiency using noninvasive hearing tests.  

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