New research in specially bred mice has elucidated how the antidepressant Prozac works. Scientists have long known that in addition to discouraging synapses from reabsorbing the neurotransmitter serotonin, Prozac (known generically as fluoxetine) also increases the number of neurons (neurogenesis) in the adult brain. But exactly how the drug manages this multiplication trick has proved difficult to pin down. Now researchers have traced the development cascade of new neurons and determined where fluoxetine exerts its multiplying--and beneficial--effect.

Grigori Enikolopov at the Cold Spring Harbor Laboratory and his colleagues bred a new strain of mice that allowed them to track the development of mature neurons from stem cells using the different marker proteins expressed. Of the six stages of neuron development observed in this process, the scientists found that more than two weeks of fluoxetine treatment boosted the number of so-called amplifying neural progenitors (ANPs) by nearly 50 percent (a migratory stream of which is shown in the image above).

Subsequent testing in mice allowed to live for a month after fluoxetine treatment showed a similar increase in the overall number of neurons. "Together, these results suggest that the fluoxetine-induced increase in the number of ANP precursors in the [brain] later translates into an increase in the number of new neurons," the researchers write in the paper presenting the findings in the Proceedings of the National Academy of Sciences.

By isolating the step in neuron development that fluoxetine influences, the scientists have identified a new target for antidepressants that may have fewer side effects. The research also unveils the links in the chain leading from stem cells to new neurons as well as provides an animal tailor-made to investigate the mechanisms of other medicines and treatments, permitting a ray of hope into the darker regions of brain dysfunction.

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