Interviewer: Fish that can repair their own brain up next on The Scope.
Announcer: Examining the latest research and telling you about the latest breakthroughs, the Science and Research Show is on The Scope.
Interviewer: I'm talking with Dr. Adam Douglass, Assistant Professor of Neurobiology and Anatomy at the University of Utah. Dr. Douglass, you have this cool result where fish basically repair their own brain. Tell me what you saw?
Dr. Douglass: In particular, we're interested in populations of neurons in the fish brain that release dopamine. So its cells that make the neurotransmitter dopamine release it into the brain and in figuring out what those cells do to behavior. Within our department, I collaborate closely with a group led by Rich Dorsky, whose lab is also interested in fish brains, but in different aspects of it, in particular, regenerative aspects of it.
The experiment that we did with Richard's lab was to ablate those neurons initially using a chemical technique that caused all of the cells, give or take a few, to disappear. What we found is that over the course of almost immediately, really, starting within a day or two of the ablation, the cells start to grow back such that by a couple of weeks after the initial insult in which we've destroyed the cell population, we have a number of neurons in the structure making dopamine that's almost identical to the number that we started with.
Interviewer: You also saw that the fish were able to regain their behavior too.
Dr. Douglass: Right. What we found is that immediately following the ablation and coincident with the loss of these dopamine neurons, the fish swim a whole lot less. If you put a group of young zebrafish, baby zebrafish into a dish, they normally swim around out pretty ruddily. They keep moving continuously and in contrast, after the ablation, the fish more or less just laid there. They could still move and, in particular, it was encouraging to see that if you startle the animals by tapping the dish or leaning over it; things that they normally don't like and try to get away from, they still swim around quite a bit. So it wasn't just a gross defect in the animal's ability to move. It seemed to be something related to its motivation to do so that was missing.
Interviewer: The fish have motivation?
Dr. Douglass: Yeah, they normally like to swim.
Interviewer: And that was able to come back over time after you . . .
Dr. Douglass: Yeah, and it came back in a way that more or less directly paralleled the regeneration of the neurons that we had killed. So while we think that there're probably other regenerative events or neurogenesis events that are ongoing in hypothalamus, some of which may have been upregulated following the ablation of these cells, the fact that the behavior comes back in a more or less proportional way relative to the number of these cells that are present makes us think that these probably are the neurons that are responsible for setting these weights, these tendencies to move or not move. And we are able to support that using other experimental techniques.
Interviewer: So you think a specific cell type regenerates and mediates this recovery. What cell type are you looking at and why is it interesting?
Dr. Douglass: The cells that we study make dopamine, this neurotransmitter which most people have heard about in the context of reward and things like addiction. It's certainly interesting in those contexts, but it turns out that dopamine does a lot of different things in human behavior as well as in fish behavior. For instance, as anybody who's learned about Parkinson's disease knows, dopamine neurons have a very important connection to locomotor behaviors, movement behaviors in every system where dopamine neurons exist.
There's also a variety of other stuff, literally dozens of different behavioral functions for this one neural transmitter. And one of the things I find interesting about this is that we have a poor ability to explain exactly how one molecule does so many different things in behavior. The answer at some level is almost certainly in the fact that there are multiple different brain regions that contain different populations of dopamine neurons. What my lab is trying to do is the relatively straightforward task of seeing what happens to behavior when you manipulate activity in these cells.
Interviewer: Do you think other cells in the brain might be able to regenerate this way as well?
Dr. Douglass: Historically, there's been this notion that brains don't grow back. Certainly the human brain . . . that its regenerative capacity that's capacity for new cell growth falls to zero following very early development. What we've come to realize over the past decades is that that's not true. It's a reasonable approximation for how the system works in the sense that neurogenesis does really fall off as you enter into adulthood and, unfortunately, cell death does increase.
But as people have looked more closely, they've realized that there are several brain areas where there's a significant amount of neurogenesis going on all the time through adulthood. That includes the area of the brain that we're studying, the hypothalamus, both in mammals and in fish exhibits lots of new cell growth.
Interviewer: Are there any implications for what this could mean for us?
Dr. Douglass: Our work is really unique in that it demonstrates not only that there's a cell population that comes back but it's a dopaminergic cell population and it's a dopaminergic cell population with a direct function in locomotor behavior. If you look at mammalian systems, unfortunately, the substantia nigra, the brain area containing dopamine neurons that are affected in Parkinson's disease, is not regenerative. That's one of the reasons that cell loss and Parkinson's ultimately leads to massive defects in locomotion and ultimately the inability to move.
Our brain area, the hypothalamus, which contains the dopamine neurons that we're studying is not functionally equivalent to the substantia nigra in a strict sense, but the fact that these neurons in fish are both connected to locomotion and have the ability to regenerate probably hold some clues as to how regeneration might be made to work in the human brain areas that are affected by neurodegenerative disease.
It's not to say that we're on the brink of having some therapeutic insight to this. That's far from the case, but I do think that it's reasonable to think that we'll learn something about how these systems work and potentially what's missing in the case of the substantia nigra dopamine neurons that makes them not able to regenerate. If you can identify those things, then that gives you potential sites for therapeutic and intervention down the line.
Announcer: Interesting, informative and all in the name of better health, this is The Scope Health Sciences Radio.
