Behavioral Disturbances as a Result of Inner Ear Defects

Inner ear defects in children can lead to a severe hearing loss.  A subset (20 – 95%) of these children also experience vestibular dysfunction pertaining to balance.  This latter condition is related to the fact that within the inner ear resides an anatomical structure referred to as the cochlea.  The cochlea serves both auditory and balance functions.

Interestingly enough, among these cases, there also exists a high incidence of behavioral issues including hyperactivity.  It has been proposed that socio-environmental factors could be risk factors that would help explain this relationship.  Another possibility is that the associated inner ear defect might directly modify brain structure and thereby result in behavioral dysfunction.

To test this hypothesis, Dr. Michelle W. Antoine and her colleagues - from the Department of Neuroscience at the Albert Einstein College of Medicine, Bronx, New York - using the mouse animal model and applying the tools available in Molecular Biology have uncovered a link between inner ear defects and discreet molecular changes within the brain.

In the genetic mouse model that was studied, the same correlation exists between inner ear defect and increased levels of hyperactivity as was found in humans.  It seems that a gene referred to as Slc12a2 is responsible for a protein product that functions as a sodium-potassium-chloride co-transporter that is expressed in many tissues including the inner ear and the central nervous system (CNS).  It is precisely this gene that is mutated in the mouse model studied.  This mutated gene is rendered non-functional.  It is therefore quite plausible that the loss of this gene could result in both inner ear defect and the behavioral disorder characterized by hyperactivity.

In attempt to further elucidate the mechanism by which motor activity is heightened in the effected mice, the investigators found that within the nucleus accumbens – an area of the mammalian brain that plays a role in fear, aggression of impulsivity – the levels of key mediators of neuronal activity were increased.  These mediators include pCREB and pERK.  In addition, hyperactivity was alleviated upon the administration of the pERK inhibitor, SL327.

These findings are of great importance; for they demonstrate that, “sensory impairment, such as inner ear dysfunction, can induce specific molecular changes in the brain that cause maladaptive behaviors, such as hyperactivity, that have been traditionally considered exclusively of cerebral origin.”