On the way to finding treatment for depression

One in every 8 people in the world lives with mental disorders, with anxiety and depressive disorder being the most common. Depression is a very complex disease, and it has many different aspects that affect it. Once we get to know more and more things about depression and its mechanisms, then in the end, we might discover new possible drugs or drug targets for treating depression. The discovery made by scientists in Estonia at the University of Tartu certainly adds a new piece to the big puzzle, which allows us to understand the mechanism of depression better.

It is estimated that only 60-70% of depressed patients are responsive to currently available antidepressant treatments. Around 40% of patients with depression do not adequately respond to antidepressant medication and one-third of patients have remission of their depressive symptoms. Of those who do not respond, 10-30% exhibit treatment-resistant symptoms. Since a large proportion of patients with depression do not respond to available drugs, it would be necessary to develop new possible drugs for the treatment of depression.

This research was part of a bigger project at the University of Tartu, Department of Physiology to study Negr1 gene and find how it links to major depressive disorder (MDD) and obesity.

“It was related to my previous work. When I joined the physiology lab in my bachelor studies, they were studying the IgLON gene family at that moment and Negr1 is one member of this gene family. First, I studied the associations between IgLON gene family members and schizophrenia, we had human brains from the Australian brain bank, and we were measuring the transcript levels of IgLON gene family members using qPCR in those brains. Negr1 was one gene that was changed in schizophrenia patients, but since in several GWAS studies Negr1 is more strongly associated with depression and body mass phenotypes we decided also to study Negr1 and its links to major depressive disorder (MDD) and obesity,” explains Maria Kaare, the main author of the study.

This study was the first to show alterations in the brain monoaminergic system in mice that had Negr1 gene deficiency. The most interesting thing that was discovered during the study was that Negr1-deficiency caused changes in the dopaminergic system of the mice. Changes in monoamine levels are one possible cause of depression. The monoamine hypothesis of depression states that monoamine neurotransmitter system dysfunction is the cause of the symptoms. Although accumulating evidence also suggests the involvement of other pathways, monoamines still play a crucial role in mood disorders and are the main targets of currently available antidepressant drugs. So, this study shows that the Negr1 gene is somehow important for the normal functioning of the dopaminergic system, at least in mice.

Mouse with Negr1- deficiency helping to solve the mysteries of depression.

Mouse with Negr1- deficiency helping to solve the mysteries of depression.

Solis BioDyne products used: FIREScript® RT cDNA Synthesis MIX and HOT FIREPol® EvaGreen® qPCR Supermix.

“I was very happy with the Solis BioDyne products, and I would definitely recommend them to others,” says Maria Kaare, PhD.

Kaare, M., Jayaram, M., Jagomäe, T., Singh, K., Kilk, K., Mikheim, K., Leevik, M., Leidmaa, E., Varul, J., Nõmm, H., Rähn, K., Visnapuu, T., Plaas, M., Lilleväli, K., Schäfer, M. K. E., Philips, M. A., & Vasar, E. (2022). Depression-Associated Negr1 Gene-Deficiency Induces Alterations in the Monoaminergic Neurotransmission Enhancing Time-Dependent Sensitization to Amphetamine in Male Mice. Brain sciences12(12), 1696. https://doi.org/10.3390/brainsci12121696