Mapping IL-1R1 expression in neurons reveals insights into brain function

Interleukin-1 (IL-1) is an important molecule involved in: inflammation It plays an important role in both healthy and diseased states. In illness, high levels of IL-1 in the brain are associated with neuroinflammation, disrupting the body's stress response, causing disease-like behavior, and activating the brain's immune cells to exacerbate inflammation. , which may allow immune cells from the body to invade the brain. . It can also cause supporting cells to produce harmful molecules, which can cause brain damage. Elevated levels of IL-1 are associated with mood disorders such as depression and problems with memory and thinking.

Conversely, under normal conditions without inflammation, IL-1 plays an important role in the brain. It regulates hormonal activity, supports healthy sleep patterns, and improves cognitive functions such as memory and learning.

IL-1R1 is like a doorbell on cells that rings when an infection or injury occurs, and in immune cells it signals the body to mount an immune response. However, neurons expressing IL-1R1 are not thought to induce inflammation, suggesting that these cells may actually integrate immune signals into neurons. It is not yet clear where and how IL-1R1 (interleukin-1 receptor type 1) controls or modifies normal brain function.

Now, a new study from Florida Atlantic University provides the most detailed and comprehensive mapping of neuronal IL-1R1 (nIL-1R1) expression in the mouse brain to date, resolving a long-standing discrepancy. Previous studies have suggested that IL-1 signaling in neurons is involved in changes in illness behavior, anxiety, and sleep, but the exact neural circuits involved have not been fully understood .

This study Neuroinflammation Journalnarrowing down the specific neuronal populations and neurotransmitter systems that may mediate these effects. Using a sophisticated cell tagging approach, researchers were able to tag a population of neurons expressing nIL-1R1, providing new insights into the functional role of this receptor in the central nervous system. I did. nervous system (CNS).

Previous research conducted by the FAU Quan Laboratory showed that chronic IL-1 signaling in glutamatergic neurons influences cognitive and social avoidance behaviors, particularly in the context of neuroinflammation and stress-related disorders. It became clear. This supports the idea that nIL-1R1 may play an important role in symptoms such as chronic stress, depression, and anxiety in the unique neural circuitry described in this study.

Using genetically engineered mice, researchers identified neurons in specific brain regions, such as the somatosensory cortex and hippocampus, that contained IL-1R1. Most of these neurons use glutamate (a neurotransmitter for signaling), but some neurons use serotonin (important for mood). They found that these IL-1R1-positive neurons are involved in circuits that control sensory processing, mood regulation, and memory.

Our study shows how specific neurons are involved in immune signals and may help explain how inflammation contributes to sensory, mood and memory impairments There is. These findings could lead to new ways to treat inflammation-related brain disorders. In terms of behavioral effects, our results support the hypothesis that nIL-1R1 signaling influences emotional and cognitive behavior. ”

Dr. Ning Quan, senior author, professor of biomedical sciences, FAU Schmidt School of Medicine, and researcher at the FAU Stiles Nicholson Brain Institute

Results revealed that nIL-1R1 expression is most prominent in the somatosensory and glutamatergic systems, areas that have been previously understudied in this field. Among the brain regions identified as expressing nIL-1R1, the dentate gyrus (DG) was consistently highlighted, reaffirming its role as a key site of neuronal IL-1R1 expression. It was done. The study also identified a thalamic relay center and various sensory cortical areas, suggesting that IL-1 signaling may play an important role in sensory processing.

“This new finding raises questions about whether immune signals influence our sensory processing and whether IL-1R1-mediated changes in sensory signals contribute to cognitive problems, anxiety, and depression. '' said lead author and postdoctoral fellow Dr. Dan Nemeth. Fellow at FAU Schmidt School of Medicine and Stiles Nicholson Brain Institute. “Furthermore, this study shows that neurons do not transmit signals in the same way as other IL-1R1-expressing cells.”

Researchers discovered IL-1R1 in neurons in brain regions associated with mood, emotion, and cognition, but an unexpected finding was that IL-1R1 is expressed in neurons in the sensory system. . Using high-tech spatial transcriptomics, they identified that IL-1R1 in neurons regulates gene pathways involved in synaptic organization without causing typical inflammation. This suggests that IL-1R1 plays a role in synaptogenesis and can modify neural circuits and their functions.

“With the most detailed mapping to date of neuronal IL-1R1 expression in the mouse brain, this study provides an unprecedented level of understanding of how IL-1 signaling influences the neural circuits that govern behavior. It brought clarity,” said Dr. Randy D. Blakely. D., co-author, Executive Director of the FAU Stiles Nicholson Brain Institute, David J. S. Nicholson Distinguished Professor of Neuroscience, and Professor of Biomedical Sciences at FAU's Schmidt School of Medicine. “This discovery opens the door to new avenues of inquiry and provides important insights into the mechanisms underlying both normal and disturbed behavioral states seen in stress-related disorders, depression and anxiety. I will.”