Sunday, 22 September 2013

Ear, ear and hyperactivity

The BBC headline - Inner ear disorders 'linked to hyperactivity' - caught my eye recently. Detailing a fascinating piece of research by Michelle Antoine and colleagues* published in the journal Science the suggestion is that issues with the inner ear that affect hearing and balance might also show some relationship with hyperactivity and in mice at least, might be amendable to treatment.
van Gogh @ Wikipedia  

Before going on, I'd like to point out that Science (the publishing journal) has produced some pretty interesting papers at a similar time to the publication of the Antoine research. I'm talking specifically about the gut bacteria from obese discordant twins producing obese mice research (see here) which discusses the 'transmissibility of obesity' among other things (see here for my previous blogging interest in this area of research). There was also that letter on MAR autism which I've covered recently....

Back to the ears - and no, not whale ears either. Apparently this is not the first time that the presence of inner ear disorders have been linked to behavioural issues as per the description from other media on this research (see here). The long-and short of the paper was the study of mice who were bred to carry a mutation in the Slc12a2 gene (see here for more information about the gene) involved with the transportation and reabsorption of sodium and chloride ions. Said mice with genetic mutation in the inner ear were observed to show "increased locomotor activity".

It was then a case of finding out why this genetic glitch produced such effects which eventually led to a part of the brain dealing with motor output: the striatum and the over-production of two proteins (pERK and pCREB) linked to the control of some important neurotransmitters: glutamate and dopamine (and GABA). Confirmation of these proteins as being involved also led to speculation that something could be done about the behaviours noted in their mouse model as per the use of a pERK inhibitor: SL327 wherein "Hyperactivity was remedied by local administration of the pERK inhibitor SL327".

I'll reiterate that as with many experimental studies these days involving knocking out genes and looking at the effects of genetic mutations, this was a study of mice and so one needs to be cautious about making too many sweeping generalisations to humans and the particular complexities that we have. I note that at least one quite prominent ADHD researcher (whose work has appeared previously on this blog) has cautioned against assuming that all ADHD is just a one gene disorder, much in the same light that autism is seemingly getting past that research hurdle too (see here).

A little light background reading on the Slc12a2 gene reveals some other interesting factoids. Schizophrenia for example, has more than one mention when it comes to looking at the expression of the gene; mainly tied back to that GABA link (see the paper by Hyde and colleagues** for example). Panichareon and colleagues*** (open-access) also detailed some potential connection between gene polymorphisms as being associated with cases of schizophrenia.

Taking into account one of the synonyms for the gene - NKCC1 - I note some mention of the drug bumetanide (see this previous post) as being involved (see here****) which 'potentially' suggests some cross-over into cases of autism too. That and the fact that hyperactivity as part of the diagnosis of ADHD may be part of the ESSENCE of at least some autism, although I hasten to add that the Antoine work did not explicitly mention autism. Ears and hearing, have been talked about previously on this blog with autism in mind though (see here and here).

I suppose the thing that really fascinates me about this work is the link between physical presentation and behavioural presentation not necessarily just exclusive to the brain in terms of origin. To me at least, it's of a similar ilk to other research; for example the observation that lower airway abnormalities might be linked with autism (see here) which still requires some follow-up. A real mind-body or body-mind connection you might say?

Some music. How about The Pixies and Here Comes Your Man.


* Antoine MW. et al. A Causative Link Between Inner Ear Defects and Long-Term Striatal Dysfunction. Science. 2013; 341: 1120-1123.

** Hyde TM. et al. Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and schizophrenia. J Neurosci. 2011 Jul 27;31(30):11088-95.

*** Panichareon B. et al. Association of CTXN3-SLC12A2 polymorphisms and schizophrenia in a Thai population. Behav Brain Funct. 2012; 8: 27.

**** Lemonnier E. & Ben-Ari Y. The diuretic bumetanide decreases autistic behaviour in five infants treated during 3 months with no side effects. Acta Paediatr. 2010 Dec;99(12):1885-8.

---------- Antoine MW, Hübner CA, Arezzo JC, & Hébert JM (2013). A causative link between inner ear defects and long-term striatal dysfunction. Science (New York, N.Y.), 341 (6150), 1120-3 PMID: 24009395