People react to stress in different ways. Some people seem to thrive under a constant deluge of deadlines, and galvanize to action in the face of life stress. In others, stress can be a trigger for psychiatric disorders such as depression, leaving them feeling helpless and causing difficulties in their everyday lives. But each person is different. So…WHAT is the difference? What makes one person respond well to stress and another shut down?
The answer, in part, may be brain derived neurotrophic factor (BDNF), one of the hot buzz-proteins being thrown around neuroscience circles these days. It’s important in depression, in drug addiction, and now, possibly, in stress resistance.
So how do you look at the effects of BDNF on stress? Well, stress some rats. We’ll start with a simple Advanced Calculus quiz…
(I love him! He’s so cute!!! Source)
Taliaz, et al. “Resilience to Chronic Stress Is Mediated by Hippocampal Brain-Derived Neurotrophic Factor” J. Neuroscience, 2011.
BDNF is a funny protein, with many roles in different areas of the brain. For instance, right now we think that decreasing BDNF in areas like the hippocampus can produce depressive-like behaviors in animals. On the other hand, decreasing BDNF in OTHER areas like the ventral tegmental area can make mice resistant to things that normally produce depression.
And all of this ties in with STRESS. In particular, it seems that the BDNF levels in the hippocampus have a good bit to do with stress. Rats exposed to chronic, mild stress show decreases in hippocampal BDNF, and also show depressive-like behaviors. But in YOUNG rats, the same mild stresses don’t produce those changes.
To look at the role that BDNF really plays in how animals respond to stress, the authors of this paper took rats and exposed them to chronic stress. This is a stress procedure that doesn’t hurt the animal, it just throws it a bunch of lifetime curveballs, kind of like sending a rat to grad school. Only instead of exams, long hours, failed projects, and poverty, you give the rat things like a 45 degree cage tilt in one direction for a while. Leave the radio on. Leave a strobe light on. Make their bedding damp. You know, the usual things that happen to you (what, your house doesn’t just tilt 45 degrees every week or so?).
But the key is: some of these rats were normal, run of the mill rats. Some of them had viruses injected into their brains that specifically increased BDNF levels in the hippocampus, and some of them had viruses injected into their brains that specifically DECREASED BDNF levels in the hippocampus. But they all got the stress.
Here are the rats that got INCREASES in BDNF with a virus in the hippocampus, and then got subjected to stress. The top graph is a measure called sucrose preference, which is used as a measure of anhedonia, or a lack of pleasure of previously pleasurable things. See, rats LOVE sugar. But stressed, depressed rats will drink less of it. You can see in the top graph that normal rats subjected to stress (third set of bars from the left) drink less sucrose than before the stress. But the rats with the artificially higher BDNF levels drank MORE sucrose (the bar on the far right). The bottom graph shows another measure of “depressive like” behavior, the forced swim test. This is a test where you put a rat (or mouse) into a beaker of water so it can’t touch the bottom. Rodents are strong swimmers and will paddle around, pawing at the walls to trying and find a way out. The test is usually 6 minutes long for mice and 15 for rats, and during that time, they will realize there’s no way out, and give up, hanging in the water. The sooner the animal gives up, and the longer it spends just floating, is thought to be a measure of depressive-like behavior. You can see in the graph that the rats who have higher levels of BDNF (far right) swam MORE than normal rats, which is thought to be “anti-depressant like”.
And how did their BDNF levels LOOK?
Well you can see that the control animals (third from the left) had a BIG decrease in BDNF, like you usually see when animals are exposed to stress. The animals who had received an artificial increase, however, showed less of a decrease, their BDNF levels were still hanging on.
So it looks like increasing BDNF in the hippocampus here can help rats be resistance to the depression-inducing effects of stress.
But what about when you LOWER the levels of BDNF?
You can see above that knocking down BDNF in the hippocampus didn’t really make the animals any MORE susceptible to stress. They reacted badly to stress, drinking less sucrose and showing some decreases in swimming behavior, but no more than the control rats. So it looks like here that increasing BDNF may help your resistance to stress, but artificially decreasing it may not hurt you (though they showed other evidence that it increased a stress response in young rats, who are normally resistant, so this might be just an adult effect.)
I think this is a neat little study. Most of the studies that you see looking at stress and BDNF look at different kinds of stress, and then look at this BDNF levels. This one went the opposite way, changing up the BDNF levels, and then looking at how the animals responded to stress. And this, and other studies looking at the relationship between stress and BDNF, has interesting implications for how we can help people who respond badly to stresses and develop depression, and could also make us look into mechanisms that increase BDNF (like exercise, for example) which could help people become more resistant to stress.
An addendum: I would like to pause and note just how much I LOVE the Journal of Neuroscience, for one very specific reason: NO SUPPLEMENTAL DATA. It’s all right there, every aspect of the story, right in the paper where you can see it, and you don’t have to go digging. Is the paper longer? Sure. But it’s worth the read and I am well pleased.
Taliaz D, Loya A, Gersner R, Haramati S, Chen A, & Zangen A (2011). Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31 (12), 4475-83 PMID: 21430148
