The teams of Odile Kellermann and of Jean-Marie Launay from Institut national de la sante et de la recherche medicale (INSERM) have revealed, for the first time, a sequence of reactions caused by Prozac at the neuron level, which contributes to an increase in the amounts of serotonin, a chemical "messenger" essential to the brain, and deficient in depressive individuals.
The two teams in close collaboration with Hoffmann-LaRoche (Basel), have now characterised in vitro and then in vivo, the various reactions and intermediate molecules produced in the presence of Prozac, which are eventually responsible for an increased release of serotonin.
This microRNA, known as miR-16, controls synthesis of the serotonin transporter.
Under normal physiological conditions, this transporter is present in the so-called "serotonergic" neurons, i.e. neurons specialised in production of this neurotransmitter.
In response to Prozac, the serotonergic neurons release a signal molecule, which causes the quantity of miR-16 to drop, which unlocks expression of the serotonin transporter in the noradrenaline neurons.
These neurons become sensitive to Prozac. They continue to produce noradrenaline, but they become mixed: they also synthesise serotonin.
Ultimately, the quantity of released serotonin is increased both in the serotonergic neurons, via the direct effect of the Prozac which prevents its recapture, and in the noradrenaline neurons through the reduction of miR-16.
Hence, "this will work has revealed, for the first time, that antidepressants are able to activate a new 'source' of serotonin in the brain", explained the researchers.
"Furthermore, our results demonstrate that the effectiveness of Prozac rests on the 'plastic' properties of the noradrenaline neurons, i.e. their capacity to acquire the functions of serotonergic neurons,"
To elucidate the mode of action of Prozac, the researchers from the Ile-de-France region used neuron stem cells, which were able to differentiate themselves into neurons for manufacturing serotonin or noradrenaline.
The findings were published in the journal Science.
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