Summary: A comprehensive study has mapped the neuronal expression of IL-1R1 (nIL-1R1) in the mouse brain, highlighting its role in sensory processing, mood and memory regulation. Researchers found that neurons expressing IL-1R1 integrate immune and neuronal signals, revealing links between inflammation and brain disorders like depression and anxiety.
The study identified key regions, such as the somatosensory cortex and hippocampus, where IL-1 signaling influences the organization of synapses and the modulation of neuronal circuits. Notably, neuronal IL-1R1 modifies synaptic pathways without triggering inflammation, suggesting distinct functions in the central nervous system.
Key facts:
- Immuno-neural connection: Neuronal IL-1R1 integrates immune signals into neuronal circuits, influencing sensory functions, mood, and memory.
- Distinct signaling channels: Unlike immune cells, IL-1R1-bearing neurons regulate synaptic organization without causing inflammation.
- Target regions: IL-1R1 expression is prominent in areas such as the hippocampus and sensory cortex, linked to mood regulation and sensory processing.
Source: FAU
Interleukin-1 (IL-1) is a key molecule involved in inflammation and plays an important role in healthy and diseased states.
In illness, high levels of IL-1 in the brain are linked to neuroinflammation, which can disrupt the body’s response to stress, cause sick-like behaviors, worsen inflammation by activating immune cells in the brain and allow the body’s immune cells to enter the brain. . It can also lead to brain damage by causing supporting cells to produce harmful molecules.
High levels of IL-1 are associated with mood disorders, such as depression, as well as problems with memory and thinking.
Conversely, under normal conditions without inflammation, IL-1 plays an essential role in the brain. It helps regulate hormonal activity, promotes healthy sleep patterns, and improves cognitive functions such as memory and learning.
IL-1R1 is like a doorbell on cells that rings when there is infection or injury, and in immune cells it signals the body to mount an immune response.
However, neurons that express IL-1R1 are not thought to induce inflammation, suggesting that these cells might actually integrate immune signals into neuronal signals. It remains to be determined where and how IL-1R1 (Interleukin-1 Receptor Type 1) may control or modify 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 long-standing inconsistencies.
Previous research has suggested that IL-1 signaling in neurons is involved in illness-related behaviors, anxiety, and sleep changes, but the exact neural circuits involved have not been well defined .
The study, published in the Journal of Neuroinflammationreduces specific neuronal populations and neurotransmitter systems that could mediate these effects.
Researchers were able to label neuronal populations that express nIL-1R1 using a smart cell-labeling approach, providing new insights into the functional roles of this receptor in the central nervous system (CNS).
Previous studies from the FAU Quan laboratory reveal that chronic IL-1 signaling in glutamatergic neurons influences cognitive and social avoidance behaviors, particularly in the context of neuroinflammation and stress-related disorders.
This supports the idea that nIL-1R1 may play a crucial role in conditions such as chronic stress, depression and anxiety in the unique neural circuits described by the present study.
Using genetically modified mice, researchers identified neurons in certain areas of the brain, such as the somatosensory cortex, hippocampus, and others, that have neuronal IL-1R1. Most of these neurons use glutamate (a neurotransmitter for signaling), while some use serotonin (important for mood).
They discovered that these IL-1R1-positive neurons are involved in circuits that control sensory processing, mood regulation and memory.
“Our study shows how certain neurons are connected to immune signals and may help explain how inflammation contributes to sensory, mood and memory disorders,” said lead author Ning Quan, Ph.D., professor of Biomedical Sciences, FAU Schmidt College of Medicine. , and a researcher at the FAU Stiles-Nicholson Brain Institute.
“These findings could lead to new ways to treat brain disorders linked to inflammation. In terms of behavioral implications, our results support the hypothesis that nIL-1R1 signaling influences emotional and cognitive behavior.
The results reveal that nIL-1R1 expression is greater in the somatosensory and glutamatergic systems, areas previously little studied in this context.
Among the brain regions identified as expressing nIL-1R1, the dentate gyrus (DG) was consistently highlighted, reaffirming its role as a key site for neuronal expression of IL-1R1.
The study also identifies thalamic relay centers and various sensory cortical regions, suggesting that IL-1 signaling may play an important role in sensory processing.
“This new finding raises the question of whether immune signals influence our sensory processing and whether IL-1R1-mediated alterations in sensory signals contribute to cognitive problems, anxiety or depression,” said Dan Nemeth. , Ph.D., first author and postdoctoral researcher. member of the FAU Schmidt College of Medicine and the Stiles-Nicholson Brain Institute.
“Additionally, this study shows that neurons do not signal in the same way as other IL-1R1-expressing cells.”
While researchers have discovered neuronal IL-1R1 in brain regions related to mood, affect, and cognition, an unexpected finding is that IL-1R1 is expressed in neurons of the sensory system .
Using high-tech spatial transcriptomics, they identified that neuronal IL-1R1 regulates genetic pathways involved in synapse organization without triggering typical inflammation. This suggests that IL-1R1 plays a role in synaptic formation and can modify neuronal circuits and their function.
“With the most detailed mapping of neuronal IL-1R1 expression in the mouse brain to date, this study provides an unprecedented level of clarity on how IL-1 signaling affects the neural circuits that govern behavior,” said co-author Randy D. Blakely, PhD, executive director of the FAU Stiles-Nicholson Brain Institute, David JS Nicholson Distinguished Professor of Neuroscience and Schmidt Professor of Biomedical Sciences FAU College of Medicine.
“The findings open the door to new avenues of exploration, providing essential insights into the mechanisms underlying normal and disrupted behavioral states observed in stress, depression and anxiety-related disorders.”
About this neuroscience research news
Author: Gisèle Galoustien
Source: FAU
Contact: Gisèle Galoustien – FAU
Picture: Image is credited to Neuroscience News
Original research: Free access.
“Brain neuronal IL-1R1 localization reveals specific neuronal circuits responsive to immune signaling” by Ning Quan et al. Journal of Neuroinflammation
Abstract
Brain neuronal IL-1R1 localization reveals specific neuronal circuits responsive to immune signaling
Interleukin-1 (IL-1) is a proinflammatory cytokine that exerts a wide range of neurological and immunological effects throughout the central nervous system (CNS) and is associated with the etiology of affective and cognitive disorders.
The related IL-1 receptor, interleukin-1 type 1 receptor (IL-1R1), is primarily expressed on non-neuronal cells (e.g., endothelial cells, choroidal cells, ependymal cells ventricular cells, astrocytes, etc.) throughout the brain. However, the presence and distribution of neuronal IL-1R1 (nIL-1R1) has been controversial.
Here, for the first time, is a new genetic mouse line that allows visualization of IL-1R1 mRNA and protein expression (Il1r1GR/GR) was used to map all brain nuclei and determine the neurotransmitter systems that express nIL-1R1 in adult male mice.
The direct responsiveness of nIL-1R1-expressing neurons to inflammatory and physiological levels of IL-1β in vivo was tested.
Neuronal expression of IL-1R1 in the brain was found in discrete glutamatergic and serotonergic neuronal populations in the somatosensory cortex, piriform cortex, dentate gyrus, and dorsal raphe nucleus.
Glutamatergic nIL-1R1 comprises the majority of nIL-1R1 expression and, using Vglut2-Cre-Il1r1r/r mice, which restrict IL-1R1 expression to only glutamatergic neurons, an atlas of glutamatergic nIL-1R1 expression in the brain was generated.
Analysis of the functional results of these nuclei expressing nIL-1R1, in both Il1r1GR/GR And Vglut2-Cre-Il1r1r/r mouse, reveals IL-1R1+ the nuclei are primarily related to sensory detection, processing, and relay pathways, mood regulation, and spatial/cognitive processing centers.
Intracerebroventricular (icv) injections of IL-1 (20 ng) induces NFκB signaling in IL-1R1+ non-neuronal cells but not in IL-1R1+ neurons, and in Vglut2-Cre-Il1r1r/r mouse IL-1 did not alter gene expression in the hippocampal dentate gyrus (DG).
GO pathway analysis of spatial RNA sequencing 1 month after restoration of nIL-1R1 in DG neurons reveals that IL-1R1 expression downregulates genes related to both synaptic function and mRNA binding while increasing selected complement markers (C1ra, C1qb).
Furthermore, DG neurons exclusively express one isoform of the IL-1R accessory protein (IL-1RAcPb), a known synaptic adhesion molecule.
Altogether, this study reveals a unique network of neurons capable of responding directly to IL-1 via nIL-1R1 via non-autonomous transcriptional pathways; pointing to these circuits as potential neural substrates for sensory, affective, and cognitive disorders triggered by immune signaling.
