How Does Chronic Inflammation Impair Cognitive Function?

A new study by researchers at King's College London, published in Nature Communications, sheds light on how chronic inflammation may contribute to cognitive decline in Alzheimer's disease, aging, depression, and the lingering neurological effects of viral infections.

The researchers found that exposing hippocampal stem cells to a molecule involved in the inflammatory response prevents them from developing into new neurons. The formation of new neurons in the hippocampus—known as hippocampal neurogenesis—is essential for learning, memory, and mood regulation. The hippocampus is one of the few regions of the adult human brain where new neurons continue to be generated throughout life. Impaired hippocampal neurogenesis has been linked to aging, neurodegenerative diseases, and mood disorders such as depression.

The study focused on cytokines, chemical signaling molecules produced by the body in response to threats such as viral infections. Cytokines trigger the immune response that helps fight infection, but persistently elevated cytokine levels are also a hallmark of chronic inflammation.

Previous research had shown that viral infections can alter the brain's ability to generate new neurons in the hippocampus. However, the precise mechanisms by which infection and inflammatory cytokines interfere with neurogenesis remained unclear.

When the researchers exposed human hippocampal stem cells to the inflammatory cytokine tumor necrosis factor alpha (TNF-α), the cells failed to mature into neurons. Instead, they entered an "immune alert" state, releasing signals that attract key immune cells known as T cells, which promote inflammation while simultaneously suppressing the production of new neurons.

Dr. Tinne A. D. Nissen, the study's first author, said: "What surprised us most was that the stem cells were not simply damaged by inflammation—they actively adopted behaviors that could sustain immune responses within the brain."

Professor Sandrine Thuret, Professor of Neuroscience at King's College London and co-author of the study, added: "Our findings reveal a new link between chronic inflammation and the brain's reduced ability to generate new neurons. Inflammatory signals appear to redirect hippocampal stem cells away from their normal role in producing neurons and toward supporting immune activity."

The researchers also identified an unexpected signaling pathway underlying this process involving type I interferons—molecules best known for their role in the body's antiviral defense. Blocking interferon signaling with an existing therapeutic antibody reversed some of the inflammatory effects by restoring neuron production and preventing the recruitment of T cells involved in the immune response.

Professor Linda C. Klavinskis, Professor of Viral Immunology at King's College London and co-author of the study, said: "Our work uncovers a new mechanism that helps explain why persistent inflammation is so damaging to brain health. It also points to potential therapeutic strategies that could protect or restore the brain's regenerative capacity."