September 5, 2013
Inner Ear Problem May Cause Hyperactivity
Brett Smith for redOrbit.com – Your Universe Online
The physiological basis for abnormal behaviors is usually found in the brain, but a new study from researchers at Albert Einstein College of Medicine in New York found that a certain type of inner ear dysfunction could increase hyperactivity through neurological changes.
"Our study provides the first evidence that a sensory impairment, such as inner ear dysfunction, can induce specific molecular changes in the brain that cause maladaptive behaviors traditionally considered to originate exclusively in the brain," said study leader Jean M. Hébert, professor of neuroscience and genetics at Albert Einstein.
The inner ear consists of the cochlea, which is responsible for hearing, and the vestibular system, which aids in balance. Inner ear disorders are usually the result of genetic defects but can also be caused by infection or injury.
The impetus for the study came from an observation made by Michelle W. Antoine, a Ph.D. student in Hébert's laboratory at the time. Antonie noticed that their lab mice were unusually active – continuously chasing their tails in a circular pattern. The researchers later discovered that the mice had significant cochlear and vestibular defects causing them to be profoundly deaf.
"We then realized that these mice provided a good opportunity to study the relationship between inner ear dysfunction and behavior," Hébert said.
The scientists found that the rodents’ inner ear problems were the result of a mutation in the gene, shared with humans, called Slc12a2, which affects the transport of sodium, potassium, and chloride molecules in various tissues, particularly the inner ear and central nervous system.
To test if the gene mutation was associated with the animals' hyperactivity, the scientists selectively deleted the Slc12a2 from either the inner ear, various parts of the brain that control movement or the entire central nervous system of healthy mice.
"To our surprise, it was only when we deleted the gene from the inner ear that we observed increased locomotor activity," Hebert said.
The researchers said that inner ear defects might cause abnormal functioning of the striatum, a brain region that controls movement. The scientists also found increased levels of two proteins involved in the action of neurotransmitters: pERK and pCREB (which is further down the signaling pathway from pERK.) Elevated levels of the two proteins were observed only in the striatum and not in other brain regions.
To see if elevated pERK levels caused the hyperactivity, Slc12a2-deficient mice were given injections of a pERK inhibitor. The inhibitor restored motor activity to normal, without affecting activity levels in the control mice. According to the researchers, the findings indicate that hyperactivity in children with inner ear disorders could be treated with medications that inhibit the pERK pathway in the striatum.
"Our study also raises the intriguing possibility that other sensory impairments not associated with inner ear defects could cause or contribute to psychiatric or motor disorders that are now considered exclusively of cerebral origin," Hébert said. "This is an area that has not been well studied."