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Researchers at Cold Spring Harbor Laboratory have identified the chief target of the widely prescribed antidepressant Prozac in the brain. This discovery might enable a new generation of more specific treatments for depression, with fewer side effects, to be developed.
It has been known for some years that Prozac (fluoxetine) is likely to relieve the symptoms of depression by somehow causing more neurons to be present in a particular region of the brain (the “dentate gyrus”). But the origins of these neurons, and how Prozac promotes their existence, have been a mystery until now. By profiling the telltale marker proteins produced by different kinds of cells in the brains of adult mice, the researchers first defined discrete steps in the complex process, called neurogenesis, that converts unspecialized stem cells into mature, specialized neurons. Next, knowing that Prozac treatment somehow increases the number of neurons in the brain, the researchers tested which step in the neurogenesis pathway might be stimulated by Prozac. They found that Prozac treatment specifically stimulates the generation of a kind of cells they dubbed “amplifying neural progenitors” or ANPs--the second step in the neurogenesis pathway from stem cells to mature neurons. The study is published in the published in the Proceedings of the National Academy of Sciences (advance on-line this week, in print on May 23). It was led by Grigori Enikolopov and spearheaded by postdoctoral fellow Juan Manuel Encinas. To address the controversy surrounding the use of Prozac in children and in pregnant women, Enikolopov’s group is currently testing the effects of the drug on brain neurogenesis in juvenile and pregnant mice. The results of those experiments may provide valuable information for assessing the possible effects of Prozac and related drugs on fetal and adolescent brain development. The researchers are currently using the approach and tools they’ve developed to explore whether other treatments for depression--including other drugs and deep brain stimulation--act in the same way as Prozac or in different ways. In addition, the scientists are screening for new drugs that expand the production of brain neurons by stimulating ANP cells to multiply. To interview the leader of the new study, contact Peter Sherwood at sherwood@cshl.edu or 516-367-6947.
Message posted by: Rashmi Nemade
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