About 20 years ago, it was demonstrated that throughout its lifetime the adult human brain can generate new neurons in certain regions. However, for a long time, the function of these "newborn neurons" has being poorly understood. Work published this week in the journal Molecular Psychiatry by the team of Alexandre Surget and Catherine Belzung (Inserm Unit 930, "Imaging and Brain", at Tours) reveals that these new neurons are indispensable to the action of antidepressants and the control of stress
Per capita, France is one of the world's major consumers of anti-depressants. Although the effectiveness of these drugs has been demonstrated, the mechanisms governing the action of these molecules are still poorly understood. Now, the team have discovered an essential clue which helps to explain how antidepressants function: It appears that everything depends on the growth of some of these new neurons and their ability to control stress
In their work, the researchers exposed mice to stress situations. The mice very quickly developed the characteristic signs of depression: weight loss, lack of interest in so-called pleasure activities (such as the discovery of a chocolate cookie), alteration in the regulation of stress hormones, etc. Moreover, unlike the others, the mice which were stressed exhibited a halt in the production of new neurons at a very specific location in the brain; namely, the hippocampus. Why is this so? This is the question that the scientists wanted to
Inspired by their initial observations, the researchers next administered Prozac to the depressed animals for several weeks and observed, in parallel, what was happening to the new neurons in the
"From a physical point of view, although the mice were still subject to stress situations, the antidepressant treatment quickly showed an effect. After several weeks both their behaviour and their level of stress hormones returned to normal. Notably, they rediscovered their taste for chocolate cookies!" declares Catherine Belzung. "However, the key discovery from our work relates to what is happening in the brain," adds the researcher.
Indeed, as surprising as it may seem, the antidepressants increase the production of new neurons. Furthermore, when X-rays were used to very specifically destroy the new neurons in the hippocampus, Prozac no longer had any effect on the mice which duly retained all the symptoms of depression.
In order to function, antidepressants depend closely on the formation of new neurons by the hippocampus. In the published article, the researchers describe how these new neurons are able to restart the endocrine stress response which is disrupted during depression. The antidepressants therefore act by stimulating the production of new neurons which, in their turn, participate in the regulation of stress which is often at the origin of depression.
"This discovery is significant and has relevance well beyond depression, because stress causes other problems such as anxiety, chronic pain and even suicide." concludes Catherine Belzung.
What are stress hormones?
In order to manage stress situations (such as the stresses of work, urban life, the loss of a close relative or friend or unemployment), the body activates a protection system based on the release of stress hormones. One of these, cortisol, has a positive effect allowing the body to find the necessary energy resources to combat the stress. However, under conditions of prolonged stress, too great a release of cortisol will have deleterious effects on the brain. Correct regulation of these stress hormones is, therefore, very
In individuals suffering from depression, the stress hormones are completely unregulated. The ineffectiveness of antidepressants for the first few days or weeks is explained by the time required to re-establish the endocrine stress system.