Apr. 15, 1999 First evidence of melatonin's role in brain plasticity
Springtime's lengthening days spark the growth of gonads and a rush of sex hormones that drive songbirds to melodic and erotic flights of fancy.
That much, scientists have known for some time.
But for the first time, scientists at The Johns Hopkins University have also identified the mysterious hormone melatonin as a critical ingredient that regulates those invigorating song bursts and fine-tunes the profound effects of testosterone on the brain.
"We think this is exciting," said Gregory Ball, a professor of psychology, who studies the interrelation of hormones, brain and behavior in song birds. "There is a lot of interest in melatonin, particularly in mammals, but there has never been any indication that it affects brain plasticity like this. The fact that it would have a direct effect on a brain area in birds and influence its volume, as we have just found, has never been addressed in other species. Perhaps one thing a study of this sort will do is encourage people to broaden their search."
The findings, co-authored by Ball and George Bentley, both of Johns Hopkins, and Thomas J. Van't Hof, of the Max Planck Institute, have just been reported in the most recent issue of the "Proceedings of the National Academy of Sciences" [full text of article available to subscribers to the journal].
About 20 years ago, it was discovered that a portion of a bird's brain involved in the control of song (known as the high vocal center, or HVC) actually increases in volume as days grow longer. Scientists realized that the regular increase in photostimulation caused by longer daylight hours in the spring is what leads to a higher level of testosterone and prompts males to sing more to attract mates and to defend against competitors. The longer daylight hours of springtime, they found, causes songbirds' gonads to grow from the size of pepper flakes to marbles. It was almost as if birds entered puberty every spring, and then the gonads shrink again every fall. Scientists were able to link the rise in testosterone to actual physical changes in the brain's HVC. But in recent years, Johns Hopkins scientists also noticed that even if songbirds are castrated, thus blocking the influence of testosterone, seasonal changes still affected the volume of HVC.
"The changes weren't as large," observed post-doctoral scientist Bentley, "but it was obvious that something else was controlling the change in volume. If it wasn't testosterone, what else could it be? Because we knew that many hormones are controlled by photoperiod, we decided to look at an obvious candidate, melatonin."
To conduct the study, European starlings without testosterone were exposed to a range of artificial daylight hours that induced reproductive states characterized by different seasons. By providing birds with melatonin, researchers found they could still have a direct effect on the HVC, reducing overall volume or otherwise attenuating its growth despite the amount of daylight.
"For example," Bentley said, "late in the summer, when birds terminate their reproductive activity and their gonads regress and testosterone disappears, the HVC doesn't really appear to shrink until later in the year. We think the effect of melatonin (which is secreted at night) is kicking in as the days get shorter, causing the volume of HVC to decrease slowly. To our knowledge, this is the first direct evidence of a role for melatonin in functional plasticity within the central nervous system of vertebrates."
Birds can be especially valuable in brain research because they exhibit radical changes in the brain in response to hormones, and scientists often are able to see a clear link between brain areas and behavior. In particular, general issues of brain plasticity, which are more difficult to assess in humans under ordinary circumstances, are much easier to investigate in birds.
"The common theme here is we can start out looking at a biological system by experimenting with birds and then we can raise questions that are of more fundamental significance to biomedical research in general," Bentley said. "We never would have discovered this if we had started out trying to see what melatonin is doing in humans. Now, with this discovery, we can feed back the information to other scientists and, perhaps, help them understand what is happening in other species."
The next step, the scientists say, is to find out just how melatonin and testosterone interact to encourage efficiency in brain volumes during breeding season. It is suspected, Bentley said, that it would be "energetically costly" to maintain a large volume of SCN year-round, and the influence of melatonin helps reduce that cost.
The study was supported by the Biotechnology and Biological Sciences Research Council Wain Fellowship scheme (United Kingdom), the National Science Foundation, and the National Institute of Neurological Disorders and Stroke.
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