This study demonstrates that abnormal glycosylation in the brain is directly linked to the onset of depression.
A surprising discovery was discovered molecular mechanism in the brain which could function as a treatment for depression.
Researchers at the Institute for Basic Science (IBS) in South Korea suggest that a tiny sugar-adding process in the brain, known as glycosylation, plays a crucial role in how stress rewires the neuronal circuits linked to depression.
The study focused on the medial prefrontal cortex (mPFC), a region of the brain involved in regulating mood.
The researchers noticed that the chronic stress it disrupts the binding of sialic acid — a sugar molecule — to proteins on the surface of neurons.
These sugar chains, glycans, are essential for regulating communication between neurons.
Although glycosylation has been studied in other studies, especially in cancer and neurodegeneration, its role in mental health has been largely neglected.
Researchers identified a key enzyme, St3gal1, responsible for the final “sugar coating” step in glycosylation. This step affects the stability of proteins and the way neurons interact at synapses.
Using high-performance mass spectrometry, the team mapped O-glycosylation patterns in nine brain regions of healthy mice, finding that each area has a unique sugar signature.
In rats subjected to chronic stress, the mPFC revealed a significant reduction in this final glycosylation step, accompanied by lower levels of St3gal1.
The enzyme turned out to be important in the study: mice without St3gal1 exhibited behaviors similar to depression, including loss of motivation and increased anxiety. On the other hand, increasing St3gal1 levels in mice subjected to stress alleviated these symptoms. The enzyme also preserves the sugar marks on neurexin-2, a protein essential for communication between neurons, which is lost under stress but is restored when St3gal1 is increased.
“This study demonstrates that the Abnormal glycosylation in the brain is directly linked to the onset of depression”, said researcher Boyoung Lee, quoted in .
It is a potential new target for diagnosis and therapy, which goes beyond traditional approaches focused on neurotransmitters.
Now the mice female reacted differently to stress, without behavioral changes in St3gal1 levels. This suggests that males and females may use distinct molecular pathways to deal with stress, offering a new direction for future studies.
This discovery could be applied not only to depression treatmentbut also the other mental illnesses, such as post-traumatic stress and schizophrenia.
