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Hyperactivity Directly Linked to Inner-Ear Disorders

Update Date: Sep 05, 2013 03:12 PM EDT

While behavioral abnormalities are often caused by problems in the brain, new research revealed that ear disorders can also alter behavior. 

Scientists at Albert Einstein College of Medicine of Yeshiva University found that inner-ear dysfunction can directly cause neurological changes that increase hyperactivity.

Experts have long known that many children and adolescents with severe inner-ear disorders also have behavioral problems.  However, until now researchers have never been able to definitively link ear disorders with behavioral problems.

Lead researcher Jean M. Hébert, Ph.D., professor in the Dominick P. Purpura Department of Neuroscience and of genetics at Yeshiva University, said the latest findings provide the first evidence that a sensory impairment like inner-ear dysfunction can trigger specific molecular changes in the brain that cause maladaptive behaviors traditionally believed to originate exclusively in the brain.

Researchers said that the idea of the study arose when they noticed that some mice in the laboratory were unusually active. Researchers said the mice were always moving and chasing their tails in a circular pattern. After examining the mice, researchers found that the animals had severe cochlear vestibular defects and were profoundly deaf.

"We then realized that these mice provided a good opportunity to study the relationship between inner-ear dysfunction and behavior," Hébert said in a news release.

Further analysis on the hyperactive mice revealed that the animals' inner-ear problems were caused by a mutation in a gene called Slc12a2, which mediates the transport of sodium, potassium, and chloride molecules in various tissues, including the inner ear and central nervous system (CNS). Researchers note that the findings may also apply to people because the gene is also found in humans.

To see if the gene mutation caused the abnormal hyperactivity in mice, researchers selectively deleted Slc12a2 from either the inner ear, various parts of the brain that control movement or the entire central nervous system in healthy mice.

"To our surprise, it was only when we deleted the gene from the inner ear that we observed increased locomotor activity," said Hébert.

The study also implicated two brain proteins that researchers say may provide potential targets for intervention and treatment.

Further analysis revealed that altering levels of the proteins pERK (phosphorylated extracellular signal-regulated kinase) and pCREB (phospho-cAMP response-element binding protein) affected hyperactivity in mice.

Researchers explained that increasing perk levels caused abnormal increase in locomotor activity in mice. However, of SL327, a pERK inhibitor, restored locomotor activity to normal, without affecting activity levels in controls.

Researchers said the latest findings suggest that hyperactivity in children with inner-ear disorders might be controllable with medications that directly or indirectly 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," said Hébert. "This is an area that has not been well studied."

The findings are published in the journal Science

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