Schizophrenia: lack of enzyme during pregnancy may be linked to the origin of the disease, says Unicamp

Schizophrenia: lack of enzyme during pregnancy may be linked to the origin of the disease Researchers from the State University of Campinas (Unicamp) and other Brazilian institutions discovered that the low activity of an enzyme during brain formation may be related to the origin of schizophrenia. The study, carried out with cells grown in the laboratory, was published in the scientific journal Glial Health Research. The research did not involve pregnant women or fetuses and, for now, does not allow us to state that the lack of the enzyme is a direct cause of the disorder. The team investigated phosphoglycerate dehydrogenase (PHGDH), an enzyme that participates in the production of serine. In the brain, this substance helps neurons communicate, grow and form connections. To understand its role in brain development, scientists reduced the activity of PHGDH while stem cells transformed into neurons and astrocytes, cells responsible, among other functions, for protecting and nourishing the brain. With the reduction of the enzyme: ? serine production decreased; ? cells started to produce and use energy differently; ?? increased neuron death; ? the extensions that connect one cell to another grew less; ? structures that simulate the developing brain have become smaller and less numerous. After 21 days, about 30% of the neurons had died. Enzyme may be linked to the origin of schizophrenia, says study Alicia Petresc/Unsplash Changes may begin during pregnancy Schizophrenia generally manifests itself in adolescence or early adulthood. The researchers, however, work with the hypothesis that the first changes occur much earlier, even during the formation of the brain in the womb. These changes would gradually affect the creation of brain communication networks. The symptoms, however, would only appear years later. "The conclusion of the work is that this enzyme is essential for neurodevelopment. During the formation of the brain, even during intrauterine life, changes occur that cause it to develop differently", stated Daniel Martins-de-Souza, a researcher at Unicamp and one of the study coordinators. The investigation began with the analysis of brain tissue from people with schizophrenia, collected after death. Scientists found abnormal amounts of PHGDH and other proteins involved in the production and use of energy by cells. As similar changes had already been observed in previous research, the team decided to investigate the enzyme's function during brain formation in more detail. SEE ALSO: Brazilian scientists create mini-brains and neurons in the laboratory to study depression The results do not mean, however, that low PHGDH activity is the only origin of schizophrenia. "We mapped hundreds of altered proteins. This result is in line with what genetic studies show: there is no single 'schizophrenia gene'", said Martins-de-Souza. A previous study by the group helps to show this complexity. In it, the researchers investigated hnRNP A1, a protein that participates in the formation and maintenance of the myelin sheath, a layer that surrounds neurons and helps in the transmission of signals in the brain. According to Martins-de-Souza, the two studies follow a similar line, but deal with different processes. While hnRNP A1 is linked to the formation of this protective layer, PHGDH acts earlier, during brain formation itself. "The first study has to do with the formation of the myelin sheath. PHGDH has a role more directly linked to neurodevelopment, to the formation of the brain", he explained. Daniel Martins-de-Souza, researcher at Unicamp and coordinator of the study Reproduction/globoplay Enzyme is also present in neurons Another finding from the study contradicts an idea consolidated in part of the scientific literature. Until then, it was believed that PHGDH was concentrated only in astrocytes. The research also identified the enzyme in forming neurons. "In fact, we saw that neurons also have this enzyme. This even changes the knowledge described in older neurobiology textbooks", stated the researcher. According to the scientists, the result indicates that neurons produce their own serine and can suffer direct damage when PHGDH activity decreases. Study still does not prove a causal relationship Although it presents evidence of a link between the enzyme, brain development and schizophrenia, the study does not prove that the reduction in PHGDH causes, in itself, the disorder. As the experiments were carried out in vitro, with cells grown in the laboratory, they do not reproduce the full complexity of a human pregnancy. "We have a strong indication of this relationship, but we still don't have definitive proof. To actually confirm it, it would be necessary to find a way to observe this process directly in the human brain", explained Martins-de-Souza. In the future, scientists want to investigate whether the lack of this enzyme also shows up in blood tests. If this is confirmed, it could act as a warning sign of the risk of the disease. It is still too early to talk about a blood test for diagnosing schizophrenia. However, the discovery could help to better understand the mechanisms of the disorder and, in the future, contribute to more precise treatments with fewer side effects. VIDEOS: everything about Campinas and the region See more news about the region on g1 Campinas