Are the neurons that manage stress involved in depression?


  • The study, conducted on mice suffering from depression, shows that chronic stress inhibits the activity of AgRP neurons, which contributes to the development of depressive behavior.
  • It is however possible to reactivate the AgrP neurons using a synthetic agonist: the depressive disorder then disappears.
  • This discovery paves the way for new, more targeted treatments for depression.

AgRP nerve cells definitely don’t have a good reputation. Already pinpointed for their role in the assimilation of food and therefore in weight gain, these neurons housed in the arcuate nucleus (NA), in the lower part of the hypothalamus, could also be involved in triggering depressive states.

This is the conclusion reached by researchers from the Medical College of Georgia (MCG) at the University of Augusta (United States). In a study published in the journal Molecular Psychiatry, they provide evidence that chronic and unpredictable stress induces changes in the function of AgRP neurons that can contribute to depression.

Chronic stress inhibition of AgRP neurons

For Dr. Xin-Yun Lu, Director of the Department of Neuroscience and Regenerative Medicine at MCG, “the small number of AgRP neurons is probably a logical target for the treatment of depression”. “It’s clear that when we manipulate these neurons, it changes behavioral responses.” However, several questions remain, such as how these AgRP neurons in the brain help us cope and adapt to chronic stress that is unpredictable over time.

To study the activity of AgRP neurons in chronic stress, the researchers worked on a mouse model suffering from depression. They found that this type of stress decreases the activity of AgRP: the latter lose their ability to activate spontaneously, which increases the activation irregularities and alters the usual activating properties of AgRP neurons.

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The researchers also used a small molecule to directly inhibit neurons. This resulted in increasing the mice’s susceptibility to chronic and unpredictable stress, and ultimately the onset of depressive behavior. By reactivating neurons, classic depressive behaviors such as hopelessness and the inability to experience pleasure disappeared.

More targeted treatments for depression

For Dr. Lu, these results are very encouraging and pave the way for the development of more targeted treatments for depression. “We can stimulate these neurons from a distance and reverse depression”, she says, explaining that it is possible to use a synthetic small-molecule agonist capable of binding to AgRP neurons to better control their activity.

This method could lead to “better ways to treat depression, including more targeted treatments that may reduce side effects, which are often severe enough to get people to stop taking them.”, continues Dr Lu, who cites weight gain and insomnia among the side effects.

While it is still unknown whether some of the existing antidepressants like Prozac impact AgRP neurons, it is possible that new therapies designed to target neurons may also cause weight gain due to the role of neurons in the neurons. eating behavior and metabolism, however, notes Dr. Lu.


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