JGU researchers seek to gain a better understanding of depression

Humans and fruit flies have little in common – at first glance. However, when studying these flies, it is actually possible to learn more about human nature, particularly when it comes to depressive disorders. On this basis, scientists at Johannes Gutenberg University Mainz (JGU) are trying to gain a better understanding of depression-like conditions and thus improve their treatment. The results were recently published in the popular journal Current Biology.

Natural materials used in traditional Asian medicine can be beneficial

We have researched the effects of natural substances used in traditional Asian medicine, such as in Ayurveda, in our area fruit fly flight model. Some of this potential could have antidepressant or preventively enhance resilience in the face of chronic stress, so that a depression-like condition does not develop.”

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

The researchers intend, among other things, to pretend effectiveness These substances, to determine their optimal formulations, isolate the actual active substances in pure form from the original plant substances. In the long term, these drugs may be marketed as generics. But there is still a long way to go – after all, this is basic research.

“In the fruit fly A model We can determine exactly where these substances are active because we are able to analyze the entire signal chain. “Moreover, each stage in the signaling path can also be demonstrated.” The researchers subjected the flies to a mild form of repeated stress, such as irregular phases of substrate vibration. This treatment results in the development of a depressive-like state (DLS) in flies, i.e. they move slower, do not stop for unexpectedly encountered sugar checks, and – unlike their more relaxed counterparts – are less willing to climb wide gaps. How does their behavior change when flies receive various natural substances? Results critically depend on the preparation of each natural substance – for example, whether it was extracted with water or alcohol.

Evening rewards can relieve depression

The research team also discovered that if they rewarded flies for 30 minutes on the evening of a stressful day, by offering food that was higher than normal, or by activating the reward signaling pathway, this could prevent the development of DLS. But what happens when the flies get a sugar reward? It was already known that flies have sugar receptors on their wrist, that is, the lower part of their legs, and their proboscis, while the end of the signaling pathway in which serotonin is released to the body of the fungus was also identified. The mushroom body is a center of associative learning in flies, which is the equivalent of the human hippocampus.

The researchers’ investigations showed that the path was much more complex than expected. Three different neurotransmitter systems must be activated in order for the deficiency of serotonin in the mushroom body, which is present in flies in DLS, to be compensated by reward. One of these three systems is the dopamine system, which also signals reward in humans. However, in light of these findings, humans should not assume that it would be OK to consume foods high in sugar accordingly. Flies see sweetness as a reward, while humans can achieve the same effect with other, healthier means.

Promote resilience by preventing depression

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


Journal reference:

Hermanns, T.; et al. (2022) Octopamine mediates the glycemic relief of a depressive-like state caused by chronic stress in fruit fly. current biology. doi.org/10.1016/j.cub.2022.07.016.

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