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Journalism of Courage
Prozac has been on the market for 18 years, yet scientists have been unable to explain much about how the popular anti-depressant works. Now, scientists at Cold Spring Harbor Laboratory in New York have figured out the intricate steps the drug—and perhaps others in its class—take to trigger the birth of neurons in the brain. It’s been known for a few years that Prozac and its chemical cousins stimulate brain cell growth, necessary for a positive effect on mood.
Understanding this mechanism could lead to the development of more effective treatments, says Grigori Enikolopov, the lead scientist in the study that appears this week in the Proceedings of the National Academy of Sciences. ‘‘This is a nice extension of previous work that shows that anti-depressants increase the birth of new neurons,’’ said Ron Duman, a professor of psychiatry and pharmacology at Yale University School of Medicine.
Duman’s group was among those that have shown the effect of neuron growth in the adult brain. But until now no one knew exactly how these medicines were doing it. Enikolopov and a postdoctoral fellow in his lab, Juan Manuel Encinas, set out to identify the pathway from a neuronal stem cell to a fully functional neuron. Many studies—in the laboratory and in animals—have shown a modest birth of neurons, about 40 percent to 50 percent.
The thinking is these new neurons are doing something to regulate memory and mood. ‘‘It is important to figure out Prozac’s target so we can develop anti-depressant drugs and other treatments,’’ Enikolopov said. The researchers had to develop a way to identify the birth of the neurons and not mistake them for other types of cells. And so they developed a new mouse tagged with a green fluorescent protein that targets the nucleus of a new neuron. ‘‘It makes it much easier to go in there and count the stem cells and their progeny,’’ Enikolopov said.
What they found when Prozac was introduced is this: One and only one cell population was targeted by the anti-depressant. And this was enough to account for the 40 percent increase in neurons in the adult brain of the animals studied. The cells are not stem cells, but the next generation of cells made by these stem cells. ‘‘It’s like a mother cell dropping its egg,’’ Enikolopov said. That is why they are called daughter cells. And in the Prozac-induced growth state, the daughter cells go through two or more divisions, giving birth to a granddaughter cell, and then a great-granddaughter cell. These steps are completed within two or three days. Then, it’s the great-granddaughter cell that slowly starts taking on the characteristics of a neuron. The process is complete within three weeks.
This finding has immediate appeal because it may provide clues as to why it takes that long for depressed patients taking these drugs to improve. The new neurons are born in an area of the brain called the dentate gyrus, part of the hippocampus. The dentate is made of neat layers. The neurons are born in the basement and migrate to the top of the dentate. There, they send projections to nearby neurons. The hippocampus regulates learning and memory, and newer studies suggest a role in mood control. (Jamie Talan)
