Yet another reason to exercise

Last weekend I went for a bike ride and when I reached the bottom of the big hill leading to UBC, I noticed quite a bit of activity going on. I didn't pay too much attention at first, but once I was booting up the hill, I was passed by several senior citizens on top-notch bicycles and I started getting curious. I asked a person who seemed to volunteer for the event what was going on. As it turns out, I was cycling right in the middle of the BC Seniors Games. Now for those of you who might not know me, my thesis research has to do with aging and the brain and nothing warms my heart like witnessing older adults and seniors exercising. I had just hit the jackpot!

The reason I'm so enthralled to see seniors exercise is because it is the single best thing they can do to preserve their brains. Today's paper highlights recent research done in California that shows just that.

First, a bit of background. You have a gene called APOE (mice also have it). It comes in 3 flavors, and each person only has one of the three: APOE2 (not important for today’s article), APOE3 and APOE4. If you got lucky and scored the APOE3 kind, all is well. If you happen to be in the 20-25% of the population who has the APOE4 kind, you may be in trouble: APOE4 is a known risk factor for Alzheimer's disease. Does it mean you'll for sure get Alzheimer’s disease? No, but you are 10 to 30 times more at risk of developing Alzheimer's disease if you carry the APOE4 gene.

In this paper, researchers compared old APOE3 (normal) and APOE4 (at risk for dementia) mice. In general, aged APOE4 mice experience cognitive decline faster and earlier than APOE3 mice. The researchers were interested in studying whether exercise (running on a mouse wheel!) had any effect on this cognitive decline.

The researchers used cognitive tasks that rely on a part of the brain that's important for memory, the hippocampus. One of the tasks, called place recognition, involves putting a mouse in an arena with two objects. The mouse is then removed from the arena, one object is moved, and the mouse is put back in the arena. Presumably, a normal mouse will then spend more time exploring the object in the new location. For this task, the aged APOE4 mice were initially impaired compared with the APOE3 mice. This means that during the second trial of the task, they tended to explore both objects for similar amounts of time, instead of spending more time on the object at the new location. This result suggests that the APOE4 were unable to remember the initial object locations well. The good news? Mice who exercised did significantly better at this task. Interestingly, this was valid for both APOE3 and APOE4 mice. Even more interestingly, exercise improved the scores of both types of mice for all the tasks that tested the hippocampus.

What's going on in the brains of these exercising mice? It is thought that exercise increases the levels of a protein called BDNF (for Brain-Derived Neurotrophic Factor). BDNF regulates many important functions in the brain, including the making of new neurons and the making of new connections between neurons, and these effects are thought to be important for memory.

Regular readers of Scientific Chick know not to get too excited when I report about animal studies. Well, I'm happy to add that the results that were observed in those mice were also observed in humans. In fact, there are countless human studies out there that confirm that physical activity is a powerful way to improve and maintain your cognitive abilities.

When I try to urge certain people to exercise (you know who you are), I almost always hear the same excuse: “Well, my uncle so-and-so never got off his couch and he lived to be 100!” In some cases, heredity can be on your side, that's true. But genetics can be quite the lottery, and it's important to keep in mind that several forms of cognitive decline, including the most common form of Alzheimer's (called “sporadic” in scientific lingo) are not hereditary.

So to all my older readers out there, I'll see you on the road at next year's BC Seniors Games. And if you're not ready for cycling, there's always the cribbage category.

Winners from this year's BC Seniors Games, cycling event. This could be you!

Reference: Exercise improves cognition and hippocampal plasticity in APOE epsilon4 mice. (2009) Nichol K, Deeny SP, Seif J, Camaclang K, Cotman CW. Alzheimers Dement. 5(4):287-94.

Children see, children do, but monkeys know better

I usually like to blog about recent articles, and I try to limit myself to papers published in the last 2-3 years. I’m going to make an exception this time and write about a publication from way back (2005). By scientific standards, 5 years ago is literally ancient (kind of like computer standards), but bear with me, this is going to be worth it (unlike a 5-year old computer).

Researchers from the UK were interested in finding out more about learning patterns, and about how our learning patterns differ from one of our close cousins, the chimpanzee. To test this, they subjected human children 2-4 years old and chimpanzees 2-6 years old to a simple task: retrieving a treat from a box.

In the first set of experiments, the researchers gave the chimps an opaque black box, and showed them how to open it to retrieve a treat inside. This wasn’t a simple pull-the-top-off kind of box, though. The box seemingly could only be opened following a series of specific steps: pulling a bolt, putting a stick in a hole, opening a door, etc. Chimps are quick-learners, though, and by imitating the researcher, they were soon able to retrieve the treat, no problem.

How well did the human children to at the same task? Quite well. They too were able to learn how to retrieve the treat from the black box by copying all the steps the researcher showed them. It would have been slightly worrying otherwise. I mean, we’ve taken over the world, right? Surely we can teach our young how to open a silly box, right?

The second set of experiments was almost exactly the same as the first one, except this time the box was made out of clear plastic instead of being opaque. The researchers went through the same process of teaching the chimps how to open the box. But there’s a catch: with a transparent box, it became very obvious that most of the steps supposedly needed to open the box were irrelevant. All you had to do was open the door. Chimpanzees, our closest living relative, are quite smart, and dropped all the unnecessary steps. They didn’t bother with the bolt and the stick and all those irrelevant actions: they went straight for the door and grabbed the treat.

When it was time for the children to be tested on the clear box, they too got shown how to open it by the researchers, including all the unnecessary steps. And when it was their turn to do it, they obviously…

Started pulling the bolt, putting the stick in the hole, etc.

Wait, what?

Did I get that wrong? I must have messed up the subjects… Wait… Nope. Those monkeys just fed us a piece of humble pie.

The researchers suggest that in the case of this study, the difference between how the chimps and how the children perform the task may have to do with a different focus of attention. Children pay more attention to the process of opening the box and the actions of the researcher, while chimps have their eyes on the prize, and focus more on the goal rather than the process. The researchers conclude by saying that imitation may be a human strategy that is often employed at the expense of efficiency.

The interesting thing about this article is that some news reports and descriptions of this experiment in magazines ended with a conclusion that more or less stipulated that our children imitated even the irrelevant steps of the task because that was the smarter thing to do, twisting the story around to make it sound like humans were superior to the chimpanzees in some way. Start your debate engines, but my opinion is that we should stop considering ourselves so superior. The results of this study are pretty straightforward. Do we really have to come up with a twisted interpretation of the results to make us sound like the winners? I would love it if we could just look at this experiment and say, hey, what do you know, we can learn something from the chimps.

Eyes on the prize, people. Eyes on the prize.

This monkey is laughing at you.

Reference: Causal knowledge and imitation/emulation switching in chimpanzees (Pan troglodytes) and children (Homo sapiens). (2005) Horner V., Whiten A. Anim Cogn 8(3):164-81.

Conquering cancer one virus at a time

Back in June, I participated in The Ride to Conquer Cancer, a 2-day bike ride between Vancouver and Seattle to raise money for BC Cancer. It was an extremely moving, positive and rewarding experience. It also gave me a chance to eat a piece of humble pie when 70 year-old cancer survivors (identified by flags on their bikes, adding to their wind resistance) would pass me going up the hill. The good news is that at the end of the 272 km, I was still smiling:

The bad news is that I didn’t conquer cancer.

Cancer research is well-funded, popular, and has been around for quite some time. So why can’t we get rid of this disease? The problem with cancer is that it’s tremendously difficult to target. Unlike cells infected by viruses and bacteria, cancer cells don’t display any obvious flags that something is wrong with them, which makes them challenging to distinguish from healthy cells. Therefore, most treatments for cancer involve killing a number of healthy cells, and that’s just not ideal.

Progress is being made, though, as a recent publication in the journal PNAS suggests. In this paper, a collaboration between researchers in California and in Japan lead to the discovery of a new way of identifying tumors for easier removal. They rely on an unlikely ally: viruses.

The researchers genetically engineered a special type of virus to carry a gene that codes for a fluorescent protein, GFP (for Green Fluorescent Protein - as simple as that!). If all the cells in your body were to be infected by that virus, you would glow (kind of like the famous puppy). While this would immediately up your popularity ranking at any science party, it doesn’t do much for treating cancer. So the researchers took it one step further and engineered the virus so that it would only express the fluorescent protein (make the cell glow) if the cell has an active telomerase. Telomerase in an enzyme involved in the replication of cells. If the telomerase enzyme is active when it shouldn’t be, it can cause cells to divide indefinitely, creating tumors. In fact, it is thought that over 90% of human tumors show telomerase activation. To sum it up, cells are infected with a virus that has a gene for a fluorescent protein, but only cancerous cells have an active telomerase, the switch that turns on the fluorescence. The result? Glowing tumors.

The benefits of these findings are two-fold. First, glowing tumors mean that surgeons can precisely remove the tumors without having to also remove a chunk of healthy tissue “just to make sure”. Second, tumors have a nasty habit of hitching a ride in your lymphatic system or your blood and disseminate throughout your body, making it very difficult to take out every little bit of sprouting tumor. With this innovation, all those little disseminated tumors can be identified and removed. Those two benefits together could greatly reduce the chance of a relapse, an important consideration when treating cancer. The researchers tested their mutant virus in two different types of animal models of cancer (colon and lung) with great success. While I’m usually worried at the prospect of glowing body parts, this research could have a big impact on cancer treatment.

If I want to give myself a chance to conquer cancer in 2010, I should probably spend less time on the computer and more time on the bike...

Glowing tumors

Reference: In vivo internal tumor illumination by telomerase-dependent adenoviral GFP for precise surgical navigation. (2009) Kishimotoa, H., Zhaoa, M., Hayashia, K., Uratad, Y., Tanakac, N., Fujiwarac, T., Penmanf, S., and Hoffmana, R.M. Proc Natl Acad Sci 106(34):14514-7.