How mice are helping with Huntington's

23 December 2013

Interview with

Dr Alisa McGregor, Auckland University

Mice are also being used to study Huntington's.  This time though, by accelerating the disease.  I spoke with Dr. Ailsa McGregor, also at Auckland University.

Ailsa -   So, our mice have also an increased CAG repeat lengths, but it's 120 Prozac pillsrepeats.  So, it's much, much more than you would see in a human patient because we need an accelerated pathology in the animals to fit with the lifespan of a mouse.

Hannah -   So, what are you seeing this mega long CAG repeats of this Huntington gene?

Ailsa -   So, we see this really classical motor impairments that human patients see.  We also see very early cognitive problems.  So, these mice are not able to learn how to do the motor test that we usually use to assess coordination in these animals.  They also really have a lot of problems with what we call delayed dependent memory.  So, can you remember this one piece of information in 5 minutes time or in a day's time?  They also are very poor in recognition memory.  So, recognizing that there is a new object in their environment.  We also look at psychiatric impairments in these animals which are much more difficult to measure, but we have ways that we can assess that type of behaviour in animal models and our transgenic mice also show a depressive like behaviour from about 6 months of age.  There is a very specific way that we look at depression in mice because they obviously can't tell you how they feel about things.  We typically use swim test and the mice will either swim or they're immobile.  In this environment, it's quite small environment and they can't generally get out.  So, we can correlate time spent immobile or floating with depression and that actually uses a screen by a lot of pharmaceutical companies to look at anti-depressant activity of new drugs.  It has a real correlate with human behaviour I guess.  So, if you imagine the time spent immobile, like despair or helplessness, we see a lot less of that after the drug treatment that we've been working on so the animals are swimming much more and they're much more active.  Another interesting correlation with human patients because other tests that we used to look at shifting strategies or cognitive tests where you have to change the way that you do something.  

Normally, we survey strategy shifting type behaviour.  It's how they find food.  They alternate between different ways of doing things.  Our Huntington's disease mice are very bad at that and they persevere with the same strategy over and over again even when it's not successful.  The types of compounds that we are interested in are involved in cholinergic transmission which is involved in attention and memory.  These compounds, even in normal mice are what we call cognitive enhancers.  So, they improve performance and memory tasks and attention to do these tasks.  We're also seeing really significant improvements in motor function in very, very elderly Huntington's disease mice.  So, we had really expected that by then we would be beyond the point where we could see any benefits, but we're actually restoring motor function in these aged Huntington's disease mice back to a normal aged mouse's performance which is great.

Hannah -   Thanks to Ailsa McGregor. 

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