Children with inner ear problems have been observed to have more behavioural problems (eg: hyperactivity).Can sensory impairments like inner ear defects directly induce brain changes that lead to behavioural dysfunction? A team of researchers (Antoine MW, Hubner CA, Arezzo JC, Hebert JM) at Albert Einstein College of Medicine of Yeshiva University in New York investigated how a mutant gene can have effect on behavioural activity levels and certain proteins in key areas in brain.
Surgical or pharmacological lesions to the vestibulo-auditory system in non human vertebrates have shown that this can lead to long-term changes in locomotor activity. Slc12a2 is a gene that encodes a sodium-potassium-chloride co-transporter broadly expressed in tissues, including the inner ear and central nervous system. Mice with mutation at this gene showed increased levels of motor hyperactivity ( locomotion, circling, and head tossing). Haloperidol can alleviate increased motor behaviour in humans, interestingly locomotor behaviour of mutant mice were also normalised with haloperidol. These observations lead the team to think that inner ear defects may cause abnormal functioning of the striatum, a central brain area that regulates motor output levels.
Researchers found that inner ear dysfunction contributes to the up- regulation of phosphorylated extracellular signal-regulated kinase (pERK1),a key component of dopamine and glutamate neurotransmission in the striatum . Increase in pERK and pCREB (phosphorylated adenosine 3′,5′-monophosphate response element–binding protein) were specific to the striatum and not observed in other forebrain regions. Total ERK and CREB were unaffected. Number of pERK- positive (pERK+) cells was up-regulated specifically in the nucleus accumbens, the ventral part of the striatum. They also found that the induction of such behaviors is inhibited by the local or systemic application of ERK kinase inhibitors, such as SL327. SL327 administration restored locomotor activity to normal levels without affecting the levels of activity in controls.
The study demonstrates that inner ear dysfunction can induce molecular changes in the striatum that promote increased motor hyperactivity. Disruption of the ERK pathway in the striatum provides a potential target for intervention.
Link between sensory impairments and behaviours is an interesting area with potential for therapeutic interventions .Extrapolating these findings to humans need to cautious at this stage.