Creating human brain circuits

20 February 2014

Interview with

Professor Mike Dragonow, Auckland University

Professor Mike Dragonow, also based at Auckland University is able to culture these stem cells from the brain bank.  As well as this, he gets brain tissue donated from epilepsy patients who've elected to have surgery to cut-out brain tissue to help control their seizures.  He harvests these tissue and grows these cells in a Petri dish, forming a brain network.  I started by asking him, how similar these cells in a dish are to a conscious, real living brain.  Can you really compare the two?

Mike -   Well, it's always a challenge actually because once you grow them in a dish, Huntingtonyou already have a very much artificial environment.  But what we can do is we can use markers for the different cell types that we know are present in the brain and see where those markers exist in the cells in the dishes, and they do.  And so, what we're trying to do really is understand how does human brain cells function their basic biology because we can test that.  so, we're looking at understanding how human brain cells that are involved in a number of neurological disorders, how they behave, their biochemistry.  And also, we're testing compounds directly on those human brain cells.  Now, one of the big problems in the neurosciences really is that compounds developed in model systems haven't actually translated to humans.  So, you have medications that work wonderfully in transgenic models of Alzheimer's disease in mice for example that kill the mice with those of Alzheimer's and yet, so far at least, none of those compounds have worked effectively in humans with Alzheimer's.  And the approach we're taking I suppose is to try and take a more direct approach if we can actually understand first the biology of the cells and secondly, use those cells to test drugs.  The drugs that work on the human brain cells in the dish may - we don't know if they will, but they may be effective in real humans that are living.  So, what we've been doing really is learning how to grow the cells, defining the different types of cells and some cells grow better than others - is that the dividing cell population that we do freeze down because they bulk up, it turns out that these dividing cells - we're not 100% sure.  We're about 95% sure now through a number of different genetic techniques in fact sorting...

Hannah -   Sorry, fac sorting.  Is that fax as in like faxing something, f transfer of information there?

Mike -   It's a sort of flow cytometry.  It allows you to actually sort cells on the basis of certain markers on this surface.  We use that to try and identify what sort of cells you have.  Using these approaches, we think that pretty sure these cells that we're growing in bulk here are called brain pericytes.  Now the pericyte actually is a very old cell, but very, very understudied, and under understood cell really because what it does, it actually lines blood vessels.  In the brain actually, there's actually a large number of pericytes and one of their functions in the brain to line blood vessels is to maintain the blood-brain barrier.  Now, this barrier is very important because molecules in the body and the blood, there are certain molecules you don't want to get into the brain.  And so, the brain has this privilege, this blood-brain barrier, the pericytes maintain the barrier and we now know through work by a number of research around the world that the blood-brain barrier breaks down in a number of neurological disorders especially in Alzheimer's.

Hannah -   So, these pericytes in this blood-brain barrier really stops any toxins entering the brain that might cause damage to the brain and therefore, cause any behavioural problems like seen in Alzheimer's or Huntington's for example.

Mike -   That's right, yes and so, people think that once that barrier breaks down, toxins can get into the brain.  They can actually add directly to the nerve cell degeneration but they can also activate immune cells in the brain to cause inflammation.  We need to study more human versions of these inflammatory cells in the brain, the microglia and the astrocytes directly.

Hannah -   Which is why it's so important to get these samples from the human brain bank tissue and also from the surgery.

Mike -   It's amazing really and our work really is driven by the amazing generosity of the patients who are undergoing surgery and also the donations that people with fatal brain disorders give to the brain bank.  It's incredible and their families.  They really drive our work and they also motivate you as a scientist.  When you're studying human brain cells, you're much more motivated to try and understand and provide some useful answers.  and so, that's our approach really, by studying human brain cells by testing drugs directly on them.  Our hope is to identify molecules that will work in humans to help reduce and stop the progression of some of these terrible disorders.

Hannah -   So, a whole host of brain disorders show an altered immune system where the brain is effectively being attacked by its body's own defence system.  Cases of Schizophrenia, Alzheimer's, and Huntington's all involve the brain being almost on fire with inflammation.  And Mike is now working on trying to come up with molecules that will dampen down this heightened inflamed response and repair the brain and hope that this will lead to new treatments for patients.

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