Brain Derived Neurotrophic Factor

(minor updates 11/2014; otherwise dated, though accurate)

Sorry the picture’s a little blurry, but it’s surprisingly old. This is the work of Duman et al, from their article presenting the “new” theory in 1997.Duman

ratBDNF (1)

What does this show? These are rat brains, cut across the middle between the ears. Sorry, there was no other way to study this and we’re lucky Dr. Duman and his colleagues have been willing to do this work for years.

The control group picture, far left, shows the brain section stained to make BDNF show dark black. You can see the part of the rat’s brain that has a lot of BDNF. This part doesn’t look at all like the human counterpart, but lo and behold, it’s the hippocampus: over and over we find this brain structure near the center of mood stories (for example, it is known to be very richly supplied with estrogen receptors, which seems to relate to the “hormones and mood” story). If you haven’t met the hippocampus, you can learn about it in humans by going to the part of this website that illustrates brain areas involved in emotion.

As you can see, the hippocampus has a lot of BDNF. But stress decreases it (2nd from left). For now we do not know how stress causes this decrease. There is a lot of evidence to suggest that stress-related steroids (cortisol, and its releasing hormone in the brain) are involved. But the point of these pictures from Dr. Duman’s research group comes in the next two photos, so let’s go on.

Look at the right two pictures. Remember these are each different rats than those whose brains appear on the left two pictures. Yet each of these two rats was subjected to the same stress as the one who shows such a decrease in BDNF. As you can see, just getting handled by the researchers enough to be given a dose of a placebo (“vehicle”) seems to have had a protective effect (at least that’s how I explained it to myself; Duman’s paper doesn’t comment on this, if I read it right). But the point of this whole thing is in the right picture. Here is the same brain section from a rat that was given Prozac (“fluoxetine”) before the same stressful task. Prozac seems to have protected this rat from the BDNF decrease seen with stress alone — more so than just getting a placebo. This is the evidence that antidepressants might even be protective against stress-related mood changes. However, you may not need to take a medication to get the same effect: read on.

Exercise and BDNF

Exercise has been repeatedly shown to increase BDNF in humans.Szuhany Even the control molecules for increased BDNF synthesis following exercise have been identified.Carro 

In the next decade (said I, in 2014), some drug company will have made a molecule that stimulates BDNF production (they’re working on that now). Won’t that be ironic: we have known that exercise is a good antidepressant for years.Phelps Just when we’re finding out that it may work through the same molecule as Prozac does, somebody’s going to come up with a pill that replaces exercise again as an antidepressant. But now that you know all this, you’re going to head out for a walk, right?

Summary

Brain derived neurotrophic factor (BDNF) may be the common pathway through which several known antidepressants have their effects. This molecule is necessary for “cell health” of hippocampal neurons. Stress decreases it, and several known antidepressant types (pills, ECT, exercise) increase it. The pills at least, and perhaps exercise (likely, in my view), can even provide protection against the BDNF decreases seen with stress. All of this understanding has come about through research led by the team of Dr. Duman at Yale University School of Medicine.

This has tremendous implications. Using this model we can think of neurons as flourishing, or shrinking back — or even dying — under the influence of stress (bad) and BDNF (good). This could change how we think about depression: not so much a change in brain chemistry (neurotransmitters at the synapse) as a change in brain architecture.

Antidepressant agents like pills, exercise and ECT work not just by changing brain chemistry, but by inducing the brain to promote its own regrowth! Finally, we see that Prozac can even protect against BDNF decreases under stress. Perhaps this is true of exercise as well, by extension? Imagine the slogans: “keep your hippocampus happy, walk a mile today” . . .