Research reveals role of microglia-neuron connections during brain development

The Laboratory of Neuroimmunology at the Institute of Experimental Medicine in Budapest (IEM), Hungary, led by Ádám Dénes, describes the presence of a site of direct interaction between microglial cells and the cell body of developing neurons, and reveals its role in brain development. The finding may be important for developmental disorders affecting the nervous system. The study (https://doi.org/10.1016/j.celrep.2022.111369) presenting the research results has been published in the prestigious Cell reports newspaper of September 20, 2022.

The scientific community knows microglia as the main immune cell of the central nervous system and as the main regulator of inflammatory processes in the brain. The role of inflammatory processes and microglia is also increasingly recognized in neurodevelopmental disorders. The study of the role of microglia in physiological and pathological conditions has become a dynamically developing area of ​​research in recent years. The research group has accumulated a significant amount of knowledge in the area of ​​microglia-neuron cell communication, and several of their publications on this topic have received international attention. They discovered a new form of communication established by direct contacts between microglia and the cell body of nerve cells, called somatic microglia-neuron junctions, and revealed the role of these specialized contact sites in protecting neurons damaged by microglia. Although the important role played by microglia during brain development has been suggested by many previous studies, the exact cellular communication pathways through which microglia influence the development of neurons and the formation of neural networks in the brain are not clear. In particular, it was not well understood how and through what types of connections developing neurons that have not yet established interaction with other neurons in the absence of synapses can receive guidance from microglial cells to develop. in complex networks in the developing neocortex.

Among the members of Ádám Dénes’ research group, Csaba Cserép and her student Dóra Anett Schwarcz played an outstanding role in the implementation of the research program, with the additional contribution of István Katona’s research group to the EMI. During their investigations, the researchers used a combination of high-resolution molecular anatomy techniques, combined light and electron microscopy, and ex vivo imaging studies. Using a multifaceted approach, the researchers demonstrated the presence of direct connections between microglia and developing neurons both during embryonic development and after birth. “The special and dynamically changing anatomical connections between microglia and developing immature neurons are similar to previously discovered somatic microglial junctions in many ways, and their special molecular composition and ultrastructure allow microglia to continuously monitor and influence effectively the development and integration of neurons into complex networks,” said Csaba Cserép, the first author of the book.

When the researchers inhibited communication via key microglial receptors that are highly enriched at these sites, the development of the normal structure of the cerebral cortex was disrupted. Therefore, microglia should be considered an important regulatory cell type of brain development via these special interaction sites and beyond. “A deeper understanding of the microglial mechanisms necessary for proper brain development can help find new therapies for neurodevelopmental disorders and other forms of brain diseases that represent an unsolved challenge worldwide,” concluded Ádám Dénes, group leader, the last author. of the publication.

Other authors included Balázs Pósfai, Zsófia I. László, Anna Kellermayer, Zsuzsanna Környei, Máté Kisfali, Miklós Nyerges, Zsolt Lele and István Katona.

Source:

Institute of Experimental Medicine, Eötvös Loránd Research Network

Journal reference:

Cserep, C., et al. (2022) Microglial control of neuronal development via somatic purinergic junctions. Cell reports. doi.org/10.1016/j.celrep.2022.111369.

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