Sunday 29 April 2012

Sulphate and the autism mouse model

I have to say that I was losing hope. I was convinced that sulphate (or sulfate if you prefer) was destined to end up as that dusty, forgotten toy under the autism research bed. Indeed a post last year all but convinced me that despite all the extremely compelling science on sulphation and autism a few years back, principally attached to Dr Rosemary Waring, sulphate was not generating the current interest that it should be.

Sulphate has however prevailed. Featuring in recent papers like this one and this one. Now further evidence that sulphate is becoming interesting again to autism research in this paper by Corley and colleagues* from the University of Hawaii and their findings based on the BTBR T+tf/J mouse model of autism.

I'm sorry that I am not able to post a link to the full-text paper, but will try and summarise the findings from this brief paper for you:

  • The BTBR T+tf/J mouse model of autism has been suggested to be one of the more 'accurate' ways of modelling certain autistic behaviours in mice in that behaviours cover the current triad of behavioural domains. This overview by McFarlane and colleagues** (full-text) provides a little more information on the model.
  • The current study simply looked at plasma sulphate levels in the BTBR T+tf/J mice compared initially with in-bred (B6) and outbred (CD-1) comparison mice. Indeed there were two experiments to this paper; the second involving a further analysis of a separate group of BTBR T+tf/J and B6 mice.
  • Age, food, water, light and other variables were constant across the groups. Gender and site and timing of blood draw were also controlled for.
  • Plasma sulphate levels were determined via a turbidimetric (cloudiness) method specifically for sulphate.
  • Significantly lower levels of plasma sulphate were observed in the BTBR T+tf/J mice compared to other strains in both experiments (p<0.05). Indeed the levels of sulphate were reduced by about 50% in the BTBR T+tf/J mice model. This was no fluke finding.

Accepting that mice and rodent models of autism, of any condition, are still open to some interpretation, these are impressive findings. I recently had an interesting discussion with a Facebook friend, Carole, about another paper using a rat model of schizophrenia (this paper) which indeed questions about whether rodent models are capable of accurately portraying autistic or schizophrenic behaviours. The answer is probably yes, at least to a degree, bearing in mind that autism in people is a mighty complex thing (and often not present in isolation).

I also hark back to the special edition of the journal Autism Research which extolled the virtues of using a mouse model for autism and defended its use as 'a' tool on the road towards examining the underlying genetic and biological processes potentially accompanying a diagnosis of autism.

I'd like to think that now that the sulphate findings have been replicated in the mouse model, a whole new chapter of sulphate chemistry with autism in mind might begin. So looking at the effects of depleted plasma sulphate on things like neurotransmitters and also the very important function of sulphate in the gastrointestinal tract (gut). I wonder also if the sulphate findings in urine might be a next step in the mouse model studies alongside what happens when sulphate is 'added' by Epsom Salt baths perhaps?

* Corley MJ. et al. Reduced sulfate plasma concentrations in the BTBR T+tf/J mouse model of autism. Physiology & Behaviour. April 2012.
DOI: 10.1016/j.physbe.2012.04.010

** McFarlane HG. et al. Autism-like behavioral phenotypes in BTBR T1tf/J mice. Genes, Brain & Behaviour. 2008; 7: 152-163

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