Neuroinflammation, a prolonged activation of the brain’s immune system prompted by infections or other factors, has been linked to the disruption of normal mental functions. Past studies, for instance, have found that neuroinflammation plays a central role in neurodegenerative diseases, medical conditions characterized by the progressive degradation of cells in the spinal cord and brain.
When inflammation is taking place, cells release proteins that act as signals between immune cells, also known as cytokines. While some studies have linked a specific cytokine called interleukin-1 (IL-1) to changes in brain function, the mechanisms through which it could contribute to a decline in mental capabilities remain poorly understood.
Researchers at the University of Toulouse INSERM and CNRS recently carried out a study involving mice aimed at better understanding these mechanisms. Their paper, published in Nature Neuroscience, particularly focused on neuroinflammation elicited by the parasite Toxoplasma gondii (T. gondii), which is responsible for a well-known illness called toxoplasmosis.
“Neuroinflammation can be triggered by infections such as SARS-CoV-2 or the parasite T. gondii,” Dr. Nicolas Blanchard, co-senior author of the paper, told Medical Xpress. “A hallmark of the latter is that it can chronically persist inside neurons of the brain, fueling chronic neuroinflammation and cognitive problems. T. gondii infection is widespread, since around one-third of the human population is expected to have been exposed to the parasite.
“The goal of this study was not only to unravel the nature of the inflammatory signals involved in Toxoplasma-induced cognitive impairments (such as deficits in spatial memory consolidation) but also to use T. gondii infection as a model to uncover the general molecular mechanisms linking neuroinflammation to neuronal dysfunction.”
The team’s recent work builds on earlier findings by the other co-senior author of the paper, Elsa Suberbielle. In her previous research, Dr. Suberbielle found evidence that spatial memory, the ability to remember the context in which we experienced something or to find our way to a specific location, relies on the delicate processes through which DNA in neurons breaks and repairs itself.
“This mechanism—called epigenetic, because it modifies the structure of DNA without changing its sequence—is essential for the optimal functioning of neurons, particularly those in the hippocampus, the brain region responsible for spatial memory,” said Dr. Suberbielle.
“In this work, we identified new links between neuroinflammatory signals (the IL-1 cytokine), the epigenetic regulation and response to DNA breaks in neurons, and the function of neuronal populations ensuring spatial memory consolidation.”
To explore the contribution of the cytokine IL-1 to the consolidation of spatial memories, Blanchard, Suberbielle and their colleagues carried out a series of experiments involving two distinct mouse models. The first of these models mimicked the chronic inflammation caused by T. gondii infection and was realized by injecting mice with the parasite.
The second model was characterized by elevated plasma levels of IL-1, which are present during various inflammatory diseases. To realize this, the team infused the cytokine IL-1 in mice via osmotic minipumps.
“We studied the importance of the IL-1 cytokine in neurons by blocking the ability of excitatory neurons (a population of neurons important for spatial memory in the hippocampus) to recognize the cytokine, through the genetic invalidation of the receptor for IL-1,” explained Dr. Blanchard.
“Consolidation of spatial memory was assessed by measuring the performance of mice in cognitive tests. More specifically, we evaluated the ability of mice to remember the position of an object, or an escape hole in a maze.”
Overall, the findings gathered by this team of researchers confirmed that infection with the T. gondii parasite disrupts the spatial memory of mice. Specifically, mice infected with the parasite struggled to remember their surroundings in detail, locate objects they had encountered before and navigate a maze.
“Our data revealed that infection with T. gondii tips the neuroinflammatory balance through an inflammatory signal: interleukin 1,” said Dr. Blanchard. “We then showed that this immune molecule alters the epigenetic regulation of neurons, providing the first molecular explanation of memory disturbances caused by this common parasite.”
In addition to shedding light on the epigenetic processes via which neuroinflammation could prompt spatial memory impairments, the researchers identified a possible strategy that could prevent these impairments. In their experiments, they showed that by blocking either the neuronal response to DNA breaks or the receptor for IL-1 inflammatory signals, they could prevent spatial memory impairments, even when the mice were experiencing high brain inflammation.
If validated in humans, these findings could have important implications for the understanding of some neurodegenerative diseases associated with memory impairments. In the future, they could also contribute to the development of new therapeutic interventions designed to prevent or reduce cognitive impairments resulting from chronic inflammation.
“Our findings extend beyond parasitic infection,” added Drs. Blanchard and Suberbielle. “Since interleukin 1 is elevated in many chronic inflammatory conditions, our study opens new avenues for treating memory-related deficits, including those seen in depression and neurodegenerative diseases.”
Written for you by our author Ingrid Fadelli, edited by Gaby Clark, —this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive.
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More information:
Marcy Belloy et al, Toxoplasma gondii infection and chronic IL-1 elevation drive hippocampal DNA double-strand break signaling, leading to cognitive deficits, Nature Neuroscience (2025). DOI: 10.1038/s41593-025-02041-x.
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