Inflammatory Reactions Caused By Microglia In The Brain Lead To Symptoms Of Depression

Depression is a depressed mental illness that can turn into aggressive, destructive, or even suicidal. Depression has been thought to be the main cause of stress due to mood, loss of interest, or joy. 

In the depressed patient’s brain, the secretion of neurotransmitters often appears to be abnormal, so only drugs that increase the secretion of neurotransmitters are used as antidepressants. However, the antidepressant drug has few disadvantages.
The mechanism of the onset of depression has not been clear yet. Tomoyuki Furuya, a researcher at the Graduate School of Medicine at Kobe University in Japan, found that inflammation caused by cells called microglia, a brain cleanser, causes symptoms of depression. 

Microglia are cells that remove foreign substances in the brain. When a sensor on its surface recognizes a foreign object, the microglia turns into an attack mode and releases an inflammatory substance called a cytokine, which causes an inflammatory reaction. 

Inflammation reaction is a phenomenon in which immune cells are activated to remove foreign substances such as pathogens and the tissue becomes hot or red. 

Until now, it has been reported that inflammation reaction occurs in the brain of depressed patients, but the causal relationship is not known. 

The mice were repeatedly stressed for 10 days, 10 minutes a day in front of the aggressive mice, which began to show signs of depression, such as avoiding other mice. 

We also investigated the brain of this depressed mouse and found that the amount of damage-related molecules increased when the cells were damaged in the area related to the control of the emotional “inner prefrontal cortex” in front of the brain. Furthermore, the amount of cytokines secreted by microglia is also beginning to increase. 

Damage-related molecules act on the TLR2 or TLR4 sensor of microglia. 

Thus, mice that were not made with these sensors in the inner frontal cortex microglias were genetically manipulated to give repeated stress.

The amount of cytokine secretion did not increase, and symptoms of depression did not appear. In other words, the microglia seem to cause the onset of depression by accepting damage-related molecules with TLR2 or TLR4 sensors to secrete cytokines (attack mode), the researchers said. 

The mechanism by which stress-related molecules are increased is still a mystery, but it is also important to identify how microglia-secreting cytokines affect neurons.

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