Neurons against Depression

Newborn neurons replaced mice with an antidepressant

In order for them to influence the behavior of the animal, they need to be "pushed"

Polina Loseva, "The Attic"

It has long been known that major depressive disorder is associated with the formation of new neurons in the brain (at least in mice): the more severe the symptoms, the fewer new arrivals. However, it is still unclear how "fresh" neurons help the brain stay afloat. A group of scientists from Chicago suggested that it's not the quantity, but the quality, or rather the activity of these cells. The researchers selectively "turned on" and "turned off" newly formed neurons in the brains of adult mice and showed that the activity of these cells itself is similar to an antidepressant. This means that you can come up with a new way to help patients with depression who are not affected by existing medications today.

In the brain of adult mammals, there are almost no stem cells left in comparison with the period of embryonic development. One of the few areas where they still exist is the hippocampus, a small area in the temporal lobe of the hemispheres involved, among other things, in the formation of memory and emotions. His work can be negatively affected by mental disorders. For example, due to a major depressive disorder, its volume decreases, and fewer new nerve cells are formed.

A research group from Chicago decided to test exactly how newly formed neurons in adult animals are associated with depression. To begin with, they found out how the antidepressant fluoxetine changes the behavior of mice. For two weeks, two groups of animals received medication or placebo, and then passed a series of standard tests: hanging by the tail (the longer the mouse hangs motionless, the more passive it is), a ring maze with light and dark areas (the more often it is in the light, the calmer) and an open field (the more often it goes to the center open space, the less disturbing). As expected, fluoxetine made the mice calmer. In addition, under its influence, neurons in their hippocampus divided more often than in animals of the control group.

Scientists have come up with a way to slow down the activity of newly formed neurons. To do this, they bred transgenic mice in which a new receptor – an analogue of the muscarinic receptor in humans – can only produce young nerve cells. The artificial receptor reacts to only one drug (clozapine-N-oxide) and interacts with the cell's own signaling pathways that block its activity. For the next experiment, the mice were already divided into 4 groups: fluoxetine + placebo, fluoxetine + blocker, placebo + blocker and double placebo. After three weeks of "treatment", the mice were tested again using behavioral tests. It turned out that a substance that inhibits young neurons completely destroys the effect of an antidepressant: mice become even more anxious and depressed than the control group.

Finally, the researchers tried to activate young neurons and brought out another group of transgenic mice in which an artificial receptor transmitted a stimulating signal to the cell, not an inhibitory one. The effect of stimulation of newborn neurons turned out to be very similar to the effect of fluoxetine: the animals spent less time motionless when they were suspended by the tail, and came closer to the center of the open maze, that is, they behaved less anxious and depressed. At the same time, neurogenesis in the hippocampus has not changed. Thus, scientists have demonstrated that the antidepressant effect arose not due to the formation of new cells by itself, but due to their activity.

Despite the fact that the controversy over neurogenesis in the human brain has not subsided yet, the authors of the work expect that their discovery can be applied to humans. Activation of young neurons, in their opinion, can become an alternative therapy for major depressive disorder for those who are not helped by already known medications. And according to some estimates, there are about a third of such patients.

Article Tunc-Ozcan et al. Activating newborn neurons suppresses depression and anxiety-like behaviors is published in the journal Nature Communications.

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