JGU researchers seek to better understand depression

Humans and fruit flies have very little in common – at first glance. However, by studying these flies, it is actually possible to learn more about human nature, especially as it relates to depressive disorders. It is on this basis that scientists from the Johannes Gutenberg University Mainz (JGU) are trying to better understand depressive states and thus improve ways of treating them. The results were published recently in the renowned journal current biology.

Natural substances used in traditional Asian medicine may prove beneficial

We have studied the effects of natural substances used in traditional Asian medicine, such as Ayurveda, in our Drosophila fly pattern. Some of them might have anti-depressive potential or prophylactically boost resilience to chronic stress, so that a depression-like state might not even develop.”


Professor Roland Strauss, JGU Institute of Developmental Biology and Neurobiology (IDN)

The researchers intend, among other things, to demonstrate the effectiveness of these substances, identify their optimal formulations and isolate the real active substances in pure form from the original plant material. In the long term, these could be marketed as drugs. But there is still a long way to go – after all, this is basic research.

“In the Drosophila model, we can identify exactly where these substances are active because we are able to analyze the entire signaling chain,” Strauss emphasized. “In addition, each step of the signaling pathway can also be proven. The researchers subject the flies to a mild form of recurrent stress, such as irregular phases of substrate vibration. ‘they move more slowly, don’t stop to examine unexpectedly encountered sugar, and – unlike their more relaxed counterparts – are less willing to scale wide gaps. How does their behavior change when the flies receive the different natural substances? The results depend decisively on the preparation of each natural substance – for example, whether it was extracted with water or alcohol.

Evening Rewards May Improve Depression

The research team also found that if they rewarded flies for 30 minutes in the evening of a stressful day, by offering them foods that were higher in sugar than usual, or by activating the reward signaling pathway, this can prevent the development of a DLS. But what happens when the flies get a sugar reward? It was already known that flies have sugar receptors on their tarsi, i.e. the lower part of their legs, and their proboscis, while the end of the signaling pathway at which serotonin is released on the body of the fungus had also been located. The fungus body is an associative learning center in flies, equivalent to the human hippocampus.

The researchers’ investigations showed that the pathway was considerably more complex than expected. Three different neurotransmitter systems must be activated until the serotonin deficiency in the fungus body, which is present in flies in a DLS, is compensated by a reward. One of these three systems is the dopaminergic system, which also signals reward in humans. In view of these results, however, humans should not assume that it would be a good idea to consume high-sugar foods as a result. Flies perceive sweetness as a reward, while humans can achieve the same effect in other, healthier ways.

Building resilience by preventing depression

In addition, the researchers decided to search for resilience factors in the fly’s genome. Just like humans, Drosophila flies have an individual genetic makeup – no two flies are the same in this regard. For this reason, the team intends to find out if and how the genomes of flies that are better able to cope with stress differ from those that develop DLS in response to exposure to recurrent mild stress. The hope is that in the future it will be possible to diagnose genetic susceptibility to depression in humans – and then treat it with the natural substances that are also being studied during the project.

Source:

Johannes Gutenberg University Mainz (JGU)

Journal reference:

Hermanns, T. et al. (2022) Octopamine mediates sugar relief from chronic stress-induced depression-like state in Drosophila. Current biology. doi.org/10.1016/j.cub.2022.07.016.

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