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Will we just be able to reverse depression in the future?
The direct activation of a gene, which is important for the excitation of our so-called excitatory neurons and is associated with severe depression, could help to reverse classic symptoms such as social isolation and loss of interest, at least in men.
In their current study, scientists from the Medical College of Georgia at Augusta University found that activation of a specific gene appears to reverse classic symptoms of depression, such as social isolation and loss of interest. The doctors published the results of their study in the English-language journal "Molecular Psychiatry".
SIRT1 activating drugs for the treatment of depression?
In their study, the experts examined the prefrontal cortex, an area of the brain that is involved in complex behaviors such as planning, personality, and social behavior. They found that when the so-called SIRT1 gene was deactivated, symptoms of depression in the male mice developed. So, if stress caused depression in real life, a drug that activates SIRT1 could reverse the symptoms, at least in men, the study authors explain. Drugs that activate SIRT1 and enable the usual high activity of excitatory neurons could one day be an effective therapy for people with severe depression, according to the experts.
SIRT1 regulates cell power plants
The delivery (firing) of signals and the communication of the neurons is clearly reduced in depression. Other diseases, such as manic behavior and seizures, on the other hand, indicate excessive signaling. Another well-known role of SIRT1 in brain cells is the regulation of cell power plants, the so-called mitochondria. The scientists found that SIRT1 in men at least partially affected the excitability of these normally excited neurons by reducing the number of cellular power plants and the expression of genes involved in power plant production. The behaviors they saw as a result of this are another indicator of the importance of SIRT1 in mood regulation. they also found that the resolution of stress-induced depression in male mice led to the activation of SIRT1, which was previously deactivated by the stress.
No comparable effects in female animals?
The experts also observed that there was apparently no effect on female mice. This was astonishing because the SIRT1 variant was first identified in a large-scale study with depressed women. The physicians suspect that physical differences in the anterior brain region, such as differences in the number of neurons and synapses between men and women, could explain the gender differences found. The scientists are already investigating whether they can find similar gender differences in the hippocampus, another brain region that plays an important role in depression and other diseases such as Alzheimer's.
Effects of anhedonia
Depressed people and depressed mice behave quite similarly. They show a so-called anhedonia, a kind of inability to feel happiness and joy. The doctors used the mice's usual preference for a sweet sucrose solution to measure their depression. When the animals are given a choice, they usually drink the solution. With anhedonia, they do not necessarily lose this preference, but their interest diminishes. Male mice also stop looking for social contact and instead become loners. They even lose interest in sex and female pheromones, the scientists explain.
What causes depression?
Existing drugs that have never been used to treat depression should now be carefully examined to determine if they have a similar effect on SIRT1 as the drug used in the study. Depression is generally caused by a combination of genetic and environmental factors. Some people are likely to be born with a variant of SIRT1 that predisposes them to depression, although environmental factors also play a role when depression occurs, the study's authors report. Such a SIRT1 variant is probably very rare and can only be associated with depression, it cannot be considered the cause. The prefrontal cortex is known to play a role in emotional responses and is involved in the control of neurotransmitters such as serotonin, which are critical for mood regulation. The severity of depression correlates with the degree of inactivity in this region of the brain, the authors of the study write.
SIRT1 gene was only discovered in women
A study published in 2015 in the journal "Nature" reported on examinations of 5,303 Chinese women with severe depressive disorders. In the investigation, the researchers identified a variant of the SIRT1 gene as one of two variants associated with the disorder. The scientists later replicated the finding in men. (as)