Link between hearing loss and autism spectrum disorder.
A multidisciplinary group of researchers from the Medical University of South Carolina has discovered a hearing impairment in a new preclinical model of autism.
Researchers at the Medical University of South Carolina (MUSC) College of Medicine report in the Journal of Neuroscience that they have observed mild hearing loss and defects in auditory nerve function in a preclinical model of autism spectrum disorder (ASD). Closer examination of the nerve tissue revealed the presence of abnormal support cells called glia, age-like degeneration, and inflammation. The results of this study highlight the importance of considering sensory organs and their interactions with the brain for understanding autism spectrum disorder
(ASD).
Many ASD patients show increased sensitivity to sound . While in the past many scientists have looked to the brain for a cause, the MUSC team took a different approach, studying the peripheral auditory system . “Hearing impairments can impact the higher-level hearing system and ultimately cognitive function,” said Hainan Lang, professor in the Department of Pathology and Laboratory Medicine at MUSC and one of the two authors of the study. study. Previous studies on age-related hearing loss have shown that the brain can increase its response to compensate for the reduction in hearing signals from the inner ear. Lang wanted to find out if this increase, calledcentral gain , could contribute to the abnormal brain response to sound in ASD. However, a significant obstacle stood in her way.
The clinically relevant model
“We did not have a clinically relevant model to directly test this important fundamental question,” said the researcher. The preclinical model that would have allowed Lang to test her hypothesis was developed in the laboratory of Christopher Cowan. The mice in this model have only one functioning 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. Interest in creating a preclinical model arose when a group of patients with ASD-like symptoms harboring MEF2C mutations was identified.
Cowan’s models also show ASD-like behaviors, including increased activity, repetitive behaviors, and communication deficits. The collaboration between Lang and Cowan began when they presented side-by-side posters at an orientation for MUSC’s College of Graduate Studies. Lang’s lab had identified molecular regulators, including MEF2C, crucial to inner ear development, and he saw Cowan’s model as something he could use to test his hypotheses about hearing loss in neurodevelopmental diseases. . Cowan eagerly agreed, and the research team began evaluating the ability to hear in MEF2C-deficient mice.
They first measured the brain’s response to auditory cues , using a modified version of a test commonly used to screen newborns for hearing loss. Mild hearing loss was observed in mice with only one functioning copy of MEF2C, while hearing remained normal in mice with two functioning 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.
The response of the auditory nerve
With their eyes on the auditory nerve, the researchers used microscopes and advanced staining techniques to determine what was wrong. Although the overall hearing loss was mild, the researchers were thrilled to see a big difference in the response of the auditory nerve. The nerves of mice with only one copy of MEF2C showed cellular degeneration similar to that seen in age-related hearing loss. The researchers also observed signs of increased inflammation, with damaged blood vessels and activated immune cells (glia and macrophages). This finding was particularly surprising to the researchers. “We now understand that auditory nerve activity can also involve the immune system, and this is the new direction we want to continue investigating,” Lang said.
“We now know that there is an important interaction between the body’s immune system and the brain’s immune system,” Cowan said. “The two systems play a fundamental role in shaping the way cells of the nervous system communicate between them, in part by eliminating excess or inappropriate connections that have formed, and this is an essential aspect of brain development and function. The results of this study could be important not only for patients with MEF2C deficiency, but also for people with DSA or hearing loss in general. “Understanding how this gene may participate in ear development and how inner ear development affects brain development has enormous applicability,” Cowan said. In future studies, the researchers plan to find out exactly how MEF2C causes the changes identified in this study. The research team also hopes to explore these findings in patients with MEF2C deficiency using non-invasive hearing testing.
