An international research group, including Hungarian scientists, has shown a direct link between the so-called P2X7 purinergic receptor in the hippocampus, which is one of the main players in inflammatory events that occur in the brain, and the growth of pyramidal cells and the formation of their projections. The discovery may be key to understanding the mechanisms underlying critical periods for normal brain development, and thus contribute to the prevention of certain neurodevelopmental disorders caused by inflammatory processes.

Publication of the discovery Journal of Neuroscience It was published in the journal ELKH Research Institute for Experimental Medicine. Researchers from the Laboratory of Molecular Pharmacology also participated in the research.

According to their explanation, neurons, called pyramidal cells after their shape, can be found in many areas of the brain and undergo many rapid changes in the early stages of life after birth. Purinergic signaling is a form of purine-mediated signaling: purines regulate cell functions by activating cell-sensitive purinergic receptors.

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Inflammatory processes play an important role in altering brain function and in the development of diseases and neurological disorders such as stroke, Alzheimer’s disease, Parkinson’s disease, epilepsy, dementia, and neurodevelopmental disorders. Among the latter, for example, autism and schizophrenia are presumed to be consequences of pathological inflammatory events that occur at critical points in brain development.

One of the main goals of the research was to see if the P2X7 receptor could be a therapeutic target in these disorders in order to reduce the propensity of adolescents and young adults to develop such conditions.

In the just-published study, the researchers sought an answer to whether P2X7R–a key player in inflammatory events that occur in the brain under pathological conditions–plays a regulatory role in the development of psychiatric disorders by examining a mouse model of schizophrenia. The researchers describe a novel role for P2X7R in a small window of time during early pregnancy, one that is essential for the proper development of pyramidal cells.

During the study, transgenic mice without the P2X7 receptor performed worse on memory tests when they were young. Abnormal activation of the P2X7 receptor, which may be a consequence of inflammatory processes during pregnancy, had a similar negative effect on neuronal development.

Similar to the deficits observed in human patients in adulthood, a tendency to impaired performance on several tests was observed in a mouse model of schizophrenia. According to the announcement, all of this illustrates the specific role of the P2X7 receptor, which requires the presence of the receptor in a perfectly balanced manner during pregnancy for healthy brain development.

The researchers demonstrated the prominent physiological and pathophysiological role of receptor activity through a versatile approach, behavioral experiments, and disease models conducted in mice. The significance of the finding is well illustrated by the fact that either blocking the receptor or pathological activation of the receptor prevents the development of the characteristic cerebral cortical architecture. Therefore, purinergic signaling should be considered as a primary therapeutic target for neurodevelopmental disorders and other diseases.

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