Can inner ear problems contribute to hyperactivity?. Science. 2013 Sep.

09.09.2013

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.

Conclusion:

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.

Comment:

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.

Summary of the article

causative link between inner ear defects and long-term striatal dysfunction.

Antoine MW, Hübner CA, Arezzo JC, Hébert JM. Science. 2013 Sep 6;341(6150):1120-3.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s