What do human brains tell us?
Now, over to Dr. Maurice Curtis, Deputy Director of this brain bank on some of the results from the samples to date.
Maurice - So, one of the things I've been interested in are the stem cells in the brain. These are cells that have the capacity to divide and become any other cell type in the whole body actually. but in this case in the brain, they would normally go on to become either glial cells which are the supporting cells of the nervous system or neurons which are kind of the active unit of the brain. These stem cells we'd would always thought were very important during the development of the brain. In fact, it's those stem cells that produce about 160 billion neurons in the course of about 4 or 5 weeks when we are developing. But once your born, the thought has always been that you don't have any more stem cells in the brain.
Hannah - So, the number of cells in your brain that you are born with, people used to think that that was it for life. So, if you have any trauma or if you do any damage to your brain then you can't replace those cells. That was the traditional hypothesis.
Maurice - That's right. That's what I was taught when I first started at the university. Only a few years later and I can still remember where I was standing when I read the paper in 1998 which indicated a paper that showed unequivocally that the brain produces new brain cells. That was staggering to me and I thought I have to know more about this. And so, we were actually interested in the Huntington's disease brain for the reason that the area that the stem cells reside is exactly next door right - they're neighbours - right next door to the area that actually degenerates in Huntington's disease. So, you've got this interesting situation where in Huntington's disease, the regenerative area and the degenerative area are neighbours. They're right next to each other. So, the areas that we're referring to when we say the stem cell area is an area called the subventricular zone that sits right next to the lateral ventricle in the brain that's the fluid-filled space in the middle of the brain. Just next to the subventricular zone is the caudate nucleus. The caudate nucleus is the area that degenerates in Huntington's disease and it normally is involved with mood and movement and hints people with Huntington's disease of problems with movement and also, they can have mood disturbances. And so, we were interested to see whether or not the area that is responsible for regenerating the brain at least during development was upregulated or whether more stem cells were born in that area, in response to the area next door, the caudate nucleus degenerating. And so, we used some special stains and what we found was that the more degeneration that was occurring in the caudate nucleus, the more regenerating cells or the more stem cells we found in the area next door the subventricular zone.
Hannah - So, it's kind of almost the opposite of what you might expect.
Maurice - Yeah, that right. So, you might naturally think it might go the other way, but if you think about how skin repairs itself, when you cut yourself, you'd think, well, that's going to kill off the cells. But actually, what it does is it gets the stem cells engaged and they come along and they appear and within a few weeks, you're left with just a small scar, but not an open wound anymore. Of course, the brain isn't nearly as able to cope with insults, but the process is similar just on a smaller scale.
Hannah - So, what's going wrong with the patients with Huntington's disease then? So, they're having more degeneration in this particular area of the brain, but they're trying to compensate with this regeneration. But why isn't it happening properly so that those regenerating cells are properly getting down into that region, making the circuits and replacing those lost cells?
Maurice - Yeah, so there's a couple of problems there I suppose that the brain has to overcome. Unlike skin which are relatively simple cells, the neurons are highly specialised, very, very specialised and they've actually done their job successfully for 40, 50, 60 years. Were then asking stem cells to come along and just replace these cells that have done their job well for a long time and asking these stem cells to find the right place to connect up with is actually quite a big ask. It's a case of too little too late. So, we don't really get the true regeneration that would be nice to be seen there.
Hannah - So, is there some genetic reason for why these new regenerating cells aren't recircuiting or getting into the circuit properly as well? Is that something to do with the genetics of Huntington's?
Maurice - We don't know that. We certainly don't have a lot of information about that. what we do know is that some of the abnormalities that occur in cells with Huntington's disease actually affects stem cells less. So for instance, the Huntington protein which abnormally accumulate in Huntington's disease, that normally is a real problem for neurons. It accumulates because the neurons are very old and they don't have such good ways of being able to get rid of those abnormal proteins, the Huntington. Stem cells, they actually don't accumulate the Huntington. Cells that are dividing don't seem to accumulate these abnormal proteins that occur later in life with diseases like Alzheimer's, Parkinson's and Huntington's. So, the stem cells seem to have a window of being immune to these problems and part of it is just the fact that they're regenerating.
Hannah - So this finding, will it lead to maybe a treatment where you can start using these stem cells which wont accumulate these misfolded or improper proteins and somehow make sure that they do make the proper connections and kind of get themselves in place in the circuit properly in order to help cure or treat Huntington's and other disorders as well like Alzheimer's?
Maurice - That's certainly always been the desire as to be able to get new cells and a cell replacement therapy essentially. What I guess we've learned from other cell replacement therapy approaches is that getting one group of cells that you put into the brain to connect up with the right target cells is actually quite tricky. It certainly has been done a lot in the past and the hope is that using endogenous stem cells, the brain can direct it themselves and we just help the brain out. So, that's certainly one of the goals. We want to know more about how is it that you actually get the brain cells to do what they would naturally do and connect up in the right places. But part of it is actually understanding what it is that drives a stem cell to make a projection to actually look for a place to connect up with elsewhere. And so, we're studying those features currently.
Hannah - Maurice Curtis on how a bank full of frozen human brains can tell us about Huntington's disease. If you would also like to donate your body and brain to research, further information and links are on our website. That's nakedscientists.com/neuroscience and have a look for the show called Naked in a brain bank.