2024-01-15 12:34:26
by Health Editorial Staff
A new chapter opens in the field of neuroimmunology, with implications for neurodevelopmental and neurodegenerative diseases
The immune system does not limit itself to protecting the brain from trauma or infections: today we know that it carries out many other functions that are fundamental to the health and functioning of the organ. Second a study published in Immunity
, the immune cells that reside in the brain (the so-called “microglial cells”) guide the development and maturation of the areas of the hippocampus responsible for memory, modifying the metabolism of the neurons that make up these areas. The study, coordinated by Michela Matteoli, full professor of Pharmacology at Humanitas University and director of the Neuroscience Program at the Humanitas Institute, adds an unprecedented piece to the knowledge of the complex relationship between immunity and the nervous system, a piece that could change our approach to various neurodevelopmental and neurodegenerative diseases.
Risk factor
«We discovered that, if the microglial TREM2 receptor does not function correctly, memory neurons in the hippocampus present anomalies in their energy metabolism during development, with implications that continue over time – explains Matteoli -. The discovery is exciting, not only because it reveals a novel function of microglial cells, but because we know that defects in the metabolism of neurons in this area are involved in several neurodegenerative diseases, including Alzheimer’s. The fact that mutations in TREM2 constitute a risk factor for the onset of the disease, as demonstrated some years ago by genetic screening studies on patients, suggests the relevance of this process.” The study was carried out in collaboration with the group of Simona Lodato, head of the Humanitas Neurodevelopment Laboratory and professor of Histology and Embryology at Humanitas University, Katia Cortese of the University of Genoa and Rafael Arguello of the CNRS of Marseille.
The TREM2 receptor
In recent years, the idea of the brain as a privileged organ from an immunological point of view, isolated from the rest of the organism, has been revolutionized: thanks to scientific research, we now know that — starting from the early stages of development up to aging — the continuous dialogue between nerve cells and immune cells guarantees the functioning of the brain and that its alterations are involved in multiple diseases. The absolute protagonists of this continuous interaction are the microglial cells and in particular the TREM2 receptor, involved in many processes and identified already in 2013 because, when mutated, it increases the risk of developing dementia and Alzheimer’s. The mechanism that links defective versions of TREM2 to the onset of Alzheimer’s is still being studied: discovering it could pave the way for the development of new therapeutic approaches for the disease.
The memory areas
The work published in Immunity, although limited to experimental models, reveals an unprecedented role of TREM2 in the formation and functioning of the areas that govern memory, those most affected by Alzheimer’s disease. «According to the results obtained in the laboratory, in the absence of TREM2 the neurons that make up the memory area in the hippocampus not only develop late, but present transcription and behavioral anomalies that persist over time, especially of a metabolic type: if it is missing TREM2 in microglia, the mitochondria of neurons (mitochondria are the “energy plants” of cells) are fewer in number and have a reduced structure and functionality – explain the first authors of the study, Erica Tagliatti and Genni Desiato -. For the first time we have demonstrated that microglial cells and their receptor TREM2 have a role in controlling the maturation of memory neurons and above all their metabolic profile.” The discovery was conducted in the laboratory and on preclinical models: further research will be necessary to understand its real implications in the study of diseases such as dementia and Alzheimer’s.
Long-term effects
Patients with genetic variants of TREM2 could have metabolism problems in the area of the brain responsible for memory, thus making it more susceptible to neurodegeneration. Not only that: the impact of the lack of TREM2, observed by researchers during development, could recur in old age, when levels of the receptor are reduced in a physiological way. «This research demonstrates once again that development and aging in the brain are two sides of the same coin and should be studied together. In recent years, for example, it has been discovered that some proteins implicated in neurodegenerative disorders play an important role already during brain development. Dysfunctional processes affecting these proteins during development can produce long-term effects, also because they affect a tissue, the nervous one, which does not undergo the continuous cellular renewal observed in other organs of the body”, concludes Michela Matteoli.
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January 15, 2024 (changed January 15, 2024 | 11:34)
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