Microglia are a group of immune cells found in the central nervous system, or CNS. These cells serve as the first line of defense of the CNS against injury, infection, and other threats. They also play a very important role in the maintenance of neuronal homeostasis, the elimination of waste and the remodeling of synapses (connections between neurons). Furthermore, in recent years, several indications of its involvement in various brain pathologies such as Alzheimer’s disease are being discovered.
The results of a new study will help to understand how neural systems with functions decisive for human behavior mature.
The study is jointly led by the Institute of Biomedicine of Seville (IBIS) affiliated with the Karolinska Institutet in Sweden as well as the University of Seville (US) in Spain and other institutions.
“Historically, microglia have been defined as brain macrophages, and thus they belong to the innate immune system,” explains José Luis Venero, professor of biochemistry and molecular biology at the University of Seville and lead researcher of the IBIS Neuronal Aging Group. Are. “Now, this is a very dynamic cell and every day it becomes more clear that this group also plays a decisive role in very important functions of the central nervous system: in the connectivity of the brain, in the regulation of neurogenesis[the appearance of]new neurons), in the regulation of neuronal excitability, etc.
During the development of the central nervous system, in the early stages known as embryonic and early postnatal, there is a connection of many neuronal systems. This ultimately forms the CNS. Microglia play a fundamental role in this process. Possible disturbances during these stages are related to neurodevelopmental disorders such as autism spectrum disorder, bipolar disorder, and various cognitive problems.
In this study, the international research team has shown how a specific subset of microglia expresses the enzyme arginase-1. For this reason the group of cells is named ARG1+ microglia. In light of research, this contributes to the establishment of the neuronal cholinergic system, which is involved in many important brain functions during early postnatal mouse development.
Using whole-brain imaging of these animals, ARG1+ microglia were found in specific regions of the developing brain, primarily in the basal forebrain and ventral striatum, where cholinergic neuron bodies are found in large numbers. The ARG1+ microglia subclass co-existed with known homeostatic microglia (ARG1-) within those brain regions, indicating that they must have intrinsic properties. Their genome sequencing analysis revealed that ARG1+ microglia display a distinct gene expression profile compared to microglia that do not express ARG1.
“Our study has identified a specific sub-population of microglia involved in the maturation of the cholinergic system,” Professor Venero stressed.
“When you have Alzheimer’s disease it takes a toll. In fact, most of the newly identified risk genes in Alzheimer’s disease are very precisely associated with microglia.” As the professor explains, this association may reveal a link between the presence of ARG1+ microglia and Alzheimer’s-like diseases.
“It remains to be seen whether the microglial population identified in our study has a direct association with the disease”, Venero contradicts on this issue. “However, according to relevant data, Alzheimer’s disease is more common in women. Interestingly, our study shows that selective deletion of a gene that marks this subpopulation (identified as arginase-1) in microglia impairs long-term memory processes, specifically in female mice. produces” according to Rocío Ruiz, a member of the research team and tenured professor at the Department of Biochemistry and Molecular Biology of the University of Seville.
The study provides a better understanding of brain development and the contribution of microglia diversity to that process, and may also provide new insights into how to manage neurodevelopmental or neurodegenerative disorders that have a cognitive component. “We must bear in mind that our study provides very relevant clues for understanding how the neural systems that play a decisive role in our behavior mature,” says the expert.
Research team member. (Photo: IBIS/US)
From accidental discovery to the future of the fight against Alzheimer’s
The research is the fruit of seven years of work and, in the words of the researcher, “represents a huge collective effort in which various national and international groups have participated.”
The work is co-directed by Dr Bertrand Joseph of the Karolinska Institutet in Sweden and José Luis Venero of the Seville Institute of Biomedicine (IBIS), and has been a collaboration of two groups from the University of Pablo de Olavid. National Level (UPO) Directed by Dr. Jose Angel Armengol and Dr. Antonio Rodriguez-Moreno.
Professor Venero emphasizes once again, “Identifying and characterizing the function of a new microglial subpopulation has been a major challenge.” “The initial identification of this subpopulation was entirely accidental. Vassilis Stratoulias, a postdoctoral student in Bertrand Joseph’s group, tested a battery of antibodies in brain tissue of young mice to detect selective labeling in areas associated with cholinergic tissue. From that moment on, the combined work to characterize its function led us to selective deletion (elimination) of the ARG1 gene in microglia cells.
Subsequent work combining techniques of transcriptomics, cell and molecular biology, behavior, electron microscopy and electrophysiology has helped the group over the past seven years to identify and understand how the ARG1+ microglial population participates in the establishment of maturation and developmental processes Is. Long term memory and learning.
“Our study reinforces the opinion about the existence of different microglial subpopulations with differentiated functions within the CNS. Microglial diversity is particularly relevant during stages of brain development. A misfunctioning of microglia can be a trigger in very important neurodevelopmental diseases or even in the etiopathology of neurodegenerative diseases such as Alzheimer’s or Parkinson’s. This research helps to open new avenues that will allow us to better understand how they arise and how we can combat them”, explains the expert.
The new study is titled “ARG1-expressing microglia show a specific molecular signature and regulate postnatal development and function of the mouse brain.” And it has been published in the academic journal Nature Neuroscience. (Source: University of Seville)