A lab mouse (spinning) demonstrates hyperactive behavior following disruption of the Slc12a2 gene. | Courtesy M.W. Antoine, C.A. Hübner, J.C. Arezzo, J.M. Hébert
New research in the 6 September issue of the journal Science hints that a genetic defect in the ear may be responsible for the hyperactive behavior seen in children with severe hearing loss.
The prevalence of hyperactivity and other behavioral problems specifically among deaf children is reported to be somewhere between 15 and 77 percent, depending on how behavior was measured and what the inclusion criteria were for different studies.
Until now, much research has focused on the socio-environmental factors behind hyperactive behaviors among children with hearing loss. But in experiments with young mice, Jean Hébert at Albert Einstein College of Medicine and colleagues found a gene in the ear linked to hyperactivity.
"We expected that the primary defect in these mice would be in the brain, so we were quite surprised to find that instead the primary defect was the ear," Hébert said in a recent podcast interview.
Hébert and colleagues created cochlear defects in the animals by knocking out a gene called Slc12a2 that is expressed in the ear. In addition to being completely deaf, the engineered animals also had a damaged vestibular system, which impaired their balance.
The deaf, wobbly mice were extremely hyperactive. The researchers found that loss of expression of Slc12a2 leads to increased levels of two proteins, pERK and pCREB, in a central part of the brain called the striatum.
When levels of pERK and pCREB become abnormally high, the striatum instructs the body to move more than it normally would, leading to hyperactivity. This scenario is like faulty electrical wiring in a house — a switch in one room accidentally turns on lights in another.
While the results offer evidence that a gene expressed in the inner ear can affect the brain in a way that causes hyperactivity, the study does not address how severe an inner ear defect must be to trigger hyperactivity. It's also unclear, the researchers said, whether the loss of hearing or the loss of the sense of balance, or both, primarily predisposes deaf animals to hyperactivity.
These findings open the door to thinking about new drug therapies that target these overactive proteins in deaf children with hyperactive behaviors.
Read the abstract, "A Causative Link Between Inner Ear Defects and Long-Term Striatal Dysfunction," by Jean Hébert and colleagues.
Listen to Jean Hébert explain the research in a AAAS Podcast