Nature: Reveals the immune memory in the brain
- Apr 16, 2018 -

In a new study, German researchers reported that inflammation in the body may affect the "memory" of immune cells in the mouse brain. If this finding is confirmed in humans, it may provide clues for the development of certain neurodegenerative diseases such as Alzheimer's disease. The results of the relevant study were published online in the journal Nature on April 11, 2018. The paper titled "Innate immune memory in the brain shapes neurological disease hallmarks".

The author of the paper, Jonas Neher, a researcher at the German Center for Neurodegenerative Diseases, said: “Epidemiological studies have shown that the infectious diseases and inflammation that you suffer in your lifetime can affect the severity of Alzheimer's disease in later life. Therefore, we Want to know whether immune memory in long-lived microglia can spread this risk."

In this study, Neher and his colleagues studied microglial cells—long-lived immune cells found only in the brain—in response to repetitive body infections. They injected a bacterial component of lipopolysaccharide into the mouse model of Alzheimer's disease to induce inflammation. The inflammatory response triggered by the first injection "trained" the microglia so that they could guard against subsequent infections. However, after repeated injections, these microglial cells hardly react - they develop resistance to bacterial lipopolysaccharide molecules.

Next, the researchers wanted to know how microglia's response to infection was related to the accumulation of amyloid plaques. In patients with Alzheimer's disease, these amyloid plaques accumulate in the brains of these patients. The Neher team found that more β-amyloid plaques accumulated in the brain of mice that received only a single injection of bacterial lipopolysaccharide compared to mice that had not received bacterial lipopolysaccharide injections. However, after these mice received four bacterial lipopolysaccharide injections, their microglia produced resistance to bacterial lipopolysaccharides, and their brains had lower levels than mice that did not receive bacterial lipopolysaccharide. Beta amyloid plaques.

Alexi Nott and Christopher Glass of the University of California, San Diego, published a news and commentary article titled “Immune memory in the brain” in the journal Nature, and wrote in the article, “This The study lays the foundation for further exploration of the influence of environmental factors on microglial function in neurodegenerative diseases."

Past studies have shown that infections and diseases such as diabetes or arthritis that can cause inflammation in humans are risk factors for Alzheimer's disease. To correlate inflammation with microglia behavior, Neher and his team sought epigenetic modifications of microglia. They found that after several months of bacterial lipopolysaccharide injection, epigenetic modifications occurred in both trained microglia and tolerogenic microglia, and these modifications correspond to differences in gene activation. This alters the function of these microglia, including their ability to engulf and destroy amyloid plaques.

Neher said: "The inflammatory diseases that are mainly produced outside the brain can trigger epigenetic reprogramming in the brain that may also be present in the human body."