(Press-News.org) Interleukin-1 (IL-1) is a key molecule involved in inflammation and plays an important role in both healthy and diseased states. In disease, high levels of IL-1 in the brain are linked to neuroinflammation, which can disrupt the body’s stress response, cause sickness-like behaviors, worsen inflammation by activating brain immune cells, and allow immune cells from the body to enter the brain. It also can lead to brain damage by causing support cells to produce harmful molecules. Elevated IL-1 levels are associated with mood disorders, such as depression, and problems with memory and thinking.
Conversely, in normal conditions without inflammation, IL-1 has essential roles in the brain. It helps regulate hormone activity, supports healthy sleep patterns, and improves cognitive functions such as memory and learning.
IL-1R1 is like a doorbell on cells that gets rung when there’s an infection or injury, and in immune cells, it signals the body to start an immune response. However, neurons that express IL-1R1 are not thought to induce inflammation, suggesting that these cells may actually integrate immune signals into neural ones. It has yet to be revealed where or how IL-1R1 (Interleukin-1 Receptor Type 1) may control or modify normal brain function.
Now, a new study by 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 sickness behaviors, anxiety, and changes in sleep, but the exact neural circuits involved have not been well-defined.
The study, published in the Journal of Neuroinflammation, narrows down the specific neuronal populations and neurotransmitter systems that could mediate these effects. Researchers were able to tag neuronal populations that express nIL-1R1 using a clever cell tagging approach, offering new insights into the functional roles of this receptor in the central nervous system (CNS).
Previous studies conducted by 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 could play a crucial role in conditions such as chronic stress, depression and anxiety in the unique neural circuits described by the current study.
Using genetically modified mice, researchers identified neurons in certain brain areas such as the somatosensory cortex, hippocampus and others, which have neuronal IL-1R1. Most of these neurons use glutamate (a neurotransmitter for signaling), while some 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 certain neurons are connected to immune signals and may help explain how inflammation contributes to sensory, mood and memory disorders,” said Ning Quan, Ph.D., senior author, professor of biomedical science, FAU Schmidt College of Medicine, and an investigator in the FAU Stiles-Nicholson Brain Institute. “These findings could lead to new ways to treat brain disorders tied to inflammation. In terms of behavioral implications, our results support the hypothesis that nIL-1R1 signaling influences emotional and cognitive behavior.”
Results reveal that nIL-1R1 expression is most prominent in the somatosensory and glutamatergic systems, areas that had previously been understudied 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 IL-1R1 expression. The study also pinpoints the thalamic relay centers and various sensory cortical regions, suggesting that IL-1 signaling could play a significant role in sensory processing.
“This new discovery opens up questions about whether immune signals influence our sensory processing and whether IL-1R1-mediated alterations of sensory signals contribute to cognitive issues, anxiety or depression,” said Dan Nemeth, Ph.D., first author and a postdoctoral fellow, FAU Schmidt College of Medicine and Stiles-Nicholson Brain Institute. “Furthermore, this study shows that neurons do not signal the same way other IL-1R1-expressing cells do.”
While researchers found neuronal IL-1R1 in brain regions related to mood, affect and cognition, an unexpected finding is that IL-1R1 is expressed in neurons in the sensory system. Using high-tech spatial transcriptomics, they identified that neuronal IL-1R1 regulates gene pathways involved in synapse organization without triggering typical inflammation. This suggests that IL-1R1 has a role in synaptic formation and can modify neural circuits and their function.
“With the most detailed mapping of neuronal IL-1R1 expression in the mouse brain to date, this study brings an unprecedented level of clarity to how IL-1 signaling impacts the neural circuits that govern behavior,” said Randy D. Blakely, Ph.D., co-author, executive director of the FAU Stiles-Nicholson Brain Institute, the David J.S. Nicholson Distinguished Professor in Neuroscience, and a professor of biomedical science in FAU’s Schmidt College of Medicine. “The findings open the door to new pathways of exploration, offering critical insights into the mechanisms underlying both normal and disrupted behavioral states seen in stress-related disorders, depression and anxiety.”
- FAU -
About Florida Atlantic University:
Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University serves more than 30,000 undergraduate and graduate students across six campuses located along the southeast Florida coast. In recent years, the University has doubled its research expenditures and outpaced its peers in student achievement rates. Through the coexistence of access and excellence, FAU embodies an innovative model where traditional achievement gaps vanish. FAU is designated a Hispanic-serving institution, ranked as a top public university by U.S. News & World Report and a High Research Activity institution by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.fau.edu.
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Our genes contain all the instructions our body needs to function, but their expression must be finely regulated to guarantee that each cell performs its role optimally. This is where DNA and RNA epigenetics comes in: a series of mechanisms that act as "markers" on genes, to control their activity without modifying the DNA or RNA sequence itself.
Until now, DNA and RNA epigenetics were studied as independent systems. These two mechanisms seemed to function separately, each playing its own role in distinct stages of the gene regulation process.
Perhaps that was a mistake.
In a publication ...
Background and objectives
No previous study has been conducted in Nigeria on the role of neutrophil elastase in predicting preterm birth. The present study aimed to determine the role of the neutrophil elastase test in predicting birth in women with preterm labor.
Methods
The present prospective cohort study recruited 83 pregnant women with preterm labor between 28 and 36+6 weeks of gestation, and followed up these subjects for 14 days. The controls comprised 85 pregnant women without preterm labor. The cervicovaginal fluid was collected and tested using the neutrophil elastase test. Then, the sensitivity, specificity, and positive and negative predictive parameters were determined. ...
WHAT:
With support from the U.S. Department of Health and Human Services (HHS) Office of the Assistant Secretary for Health (OASH), the National Institutes of Health (NIH) is leading the implementation of the Dr. Emmanuel Bilirakis and Honorable Jennifer Wexton National Plan to End Parkinson’s Act (P.L. 118-66), which was signed into law on July 2, 2024. This follows a delegation of authority from the Secretary of the Department of Health and Human Services to the NIH Director.
The act establishes a Federal ...
About The Study: In this cross-sectional study, nearly one-half of all primary care physicians (PCPs) were affiliated with hospitals, while private equity-affiliated PCPs were growing and concentrated in certain regional markets. Relative to PCPs in independent settings, hospital-affiliated PCPs and private equity-affiliated PCPs had higher prices for the same services.
Corresponding Author: To contact the corresponding author, Yashaswini Singh, PhD, MPA, email yashaswini_singh@brown.edu.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamahealthforum.2024.4935)
Editor’s ...
About The Study: This cross-sectional study showed websites that sell compounded glucagon-like peptide-1 receptor agonists (GLP-1 RAs) often partially informed and sometimes misinformed potential consumers. Compounded medications contain the same active ingredients as in branded medications but may contain different inactive ingredients. Most websites did not disclose that compounded GLP-1 RAs were not FDA approved, although some suggested these drugs were FDA approved. Many websites provided limited safety information and unauthorized efficacy claims. Some ...
About The Study: This study found modest evidence of reductions in out-of-pocket costs and improvements in health among adults entering Medicare after the Affordable Care Act. Insurance coverage and financial assistance should be preserved and enhanced to improve health and health care access among vulnerable older adults.
Corresponding Author: To contact the corresponding author, Renuka Tipirneni, MD, MSc, email rtipirne@med.umich.edu.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamahealthforum.2024.5025)
Editor’s ...
With more than 50,000 described species, the leaf beetle family is distributed worldwide and represents about a quarter of the species diversity of all herbivores. Leaf beetles can be found to feed on almost all plant groups. They live in the rhizosphere, the canopy and even underwater. Many leaf beetles, such as the Colorado potato beetle, are notorious pests. Their species richness and global distribution highlight their evolutionary success, which is particularly astonishing given that leaves are a difficult food source to digest and provide unbalanced nutrients.
Researchers from the Department of Insect Symbiosis at the Max Planck Institute for Chemical ...
Individuals with sickle cell disease – a chronic illness where misshapen, sticky blood cells clump together, reducing oxygen delivery to organs – are at a higher risk for stroke and resulting cognitive disability. But even in the absence of stroke, many such patients struggle with remembering, focusing, learning and problem solving, among other cognitive problems, with many facing challenges in school and in the workplace.
Now a multidisciplinary team of researchers and physicians at Washington University School of Medicine in St. Louis has published a study that helps explain how the illness might affect cognitive performance ...
The diversity of plasma research at the U.S. Department of Energy’s (DOE) Princeton Plasma Physics Laboratory (PPPL) was readily apparent when the PPPL 2024 Distinguished Research Fellows were recently announced. Elena Belova and Yevgeny Raitses were awarded the honor at the Lab’s annual State of the Laboratory event. Belova, a theoretical physicist, won for her work developing highly complex simulations of plasmas in different fusion experiments. Raitses, a managing principal research physicist, was honored for his experimental work on ...
Background and Aims
The transcription factor sex-determining region Y-related high-mobility group-box gene 9 (SOX9) plays a critical role in organ development. Although SOX9 has been implicated in regulating lipid metabolism in vitro, its specific role in metabolic dysfunction-associated steatohepatitis (MASH) remains poorly understood. This study aimed to investigate the role of SOX9 in MASH pathogenesis and explored the underlying mechanisms.
Methods
MASH models were established using mice fed either a methionine- and choline-deficient (MCD) diet or a high-fat, high-fructose diet. To evaluate the effects of SOX9, hepatocyte-specific SOX9 deletion or overexpression was performed. ...
