Khaberni - Chronic stress reprograms the brain, causing mental health problems. Scientists currently believe that adding sugar may act as a converter for depression, representing a new approach to understanding mood disorders and treatment methods, according to New Atlas, citing the journal Science Advances.
Scientists from the Korea Institute of Basic Science have found that prolonged stress changes how proteins in the medial prefrontal cortex (mPFC) are "decorated" with sialic acid, a sugar molecule that helps form the surface properties of neuronal cells. These sugar chains, called glycans, are linked after protein formation, in a process known as "glycosylation." Glycosylation has been studied in terms of its impact on cancer development, and more recently, on neurodegeneration.
Molecular Sugar Coating
In a type of glycosylation known as oxygen-linked glycosylation, sugars are bound to oxygen atoms in specific amino acids in the protein. This "molecular sugar coating" helps regulate how nerve cells connect and signal to each other.
Until recently, this aspect was largely overlooked in mental health research, but scientists have discovered that stress can affect these sugar patterns, potentially reprogramming "normal" communication between brain cells.
In this study, researchers identified that a single enzyme, St3gal1, performs the final step in the "sugar coating" process, and this small, yet integral phase affects the duration of protein presence and how they interact at synaptic junctions, leading, if this interaction is hindered, to depression-like behaviors.
Stress Effect
Stress leads to a significant decrease in the sugar coating step associated with oxygen interaction, and a corresponding decrease in St3gal1 expression. Disabling the St3gal1 enzyme can result in symptoms of depression, including loss of motivation and increased anxiety. Conversely, increasing St3gal1 enzyme levels has the opposite effect, alleviating these behaviors.
Laboratory mice experiments have shown that this enzyme plays a major role in how stress induces depression-like changes in the brain. Researchers have also discovered that St3gal1 helps maintain sugar markers on neurexin-2, a protein that supports communication between nerve cells.
Direct Link to Depression Onset
Researcher Boyoung Lee said, "This study shows that abnormal glycosylation in the brain is directly linked to the onset of depression, and this research provides a critical foothold for identifying new diagnostic markers and therapeutic targets beyond neurotransmitters."
While many current antidepressants affect serotonin by increasing its levels or altering its signals, there is increasing evidence that the issue is not just a serotonin deficiency.
Interestingly, female laboratory mice exposed to chronic stress exhibited behavioral changes, but their St3gal1 levels did not change, suggesting that males and females may rely on different molecular pathways to cope with stress. Therefore, these findings open up a new field of research.
