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Science is gradually piecing together the vexing brain puzzle that connects depression and inflammation, and an important new piece just fell into place. Researchers using a mouse model have discovered how stress triggers an immune response in the brain that leads to inflammation and ultimately depression – and the implications for humans could eventually be big.

Clues linking inflammation and depression have been appearing in studies for the better part of a decade, but the “how and why” hasn’t been easy to identify. For example, while it’s now clear that depression and brain-tissue inflammation often appear in tandem, it’s not clear whether depression leads to inflammation or the other way around.

The latest study may provide part of the answer. Researchers found that by genetically manipulating particular immune receptors in the brains of mice, they could control how their brains reacted to stress. When they allowed the mice brains to be affected by repeated bouts of stress, they were able to witness an immune response that triggered the release of cytokines – proteins that serve as a marker of inflammation in both mice and humans. That inflammatory response, in turn, led to “the atrophy and impaired response of neurons in the medial prefrontal cortex [part of the brain's executive control center], causing depressive behavior.”

In other words, the researchers were able to observe a series of falling dominoes starting with stress, leading to inflammation, leading to depression, all playing out through an immune response in the brain.

“These findings demonstrate the importance of neural inflammation caused by the innate immune system for stress-induced depression,” said lead researcher Professor Tomoyuki Furuyashiki at the Kobe University Graduate School of Medicine in Japan.

Results from a study earlier this year showed that more than a decade of untreated depression is linked to higher levels of inflammation in the human brain, which su

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