Institute of Biology expands the view on the disease, which affects 1,7% of the Brazilian population
Unicamp researchers studying schizophrenia are increasingly certain that the cause of the disease is related to a brain cell called an oligodendrocyte, and not to the neuron, until now the main focus of investigations by the scientific community around the world. “Schizophrenia may not be a disease of the neuron, but of the oligodendrocyte”, emphasizes Professor Daniel Martins-de-Souza, head of the Neuroproteomics Laboratory at the Institute of Biology (IB).
Using human brain tissue collected from patients after death, and cell cultures, the laboratory team discovered a flaw in the oligodendrocyte's energy metabolism. The cell is responsible for the formation of the myelin sheath that surrounds the axon, the part of the neuron equivalent to an “arm”, which connects to another neuron at a synapse. Myelin “covers” the axon and prevents the loss of energy in the transmission of impulses from one neuron to another. “If you don't have a good 'cover', transmission stops occurring correctly. This is what happens in schizophrenia. Studies indicate that the root of the problem is oligodendrocytes”, highlighted Daniel.
Three researchers from the laboratory have work directly related to the topic and have been publishing the group's findings in several complementary articles. There is papers published in the journals Schizophrenia Research, Journal of Psychiatric Research, Journal of Proteome Research and Molecular Neuropsychiatry, among others. Doctoral students Verônica Saia-Cereda, Giuliana Zuccoli and doctoral student Guilherme Reis-de-Oliveira participated in the interview with Jornal da Unicamp.
Verônica explained that the oligodendrocyte, in addition to being responsible for myelination, energetically supports neurons through a biochemical pathway that is glycolysis. The energy generated in glycolysis by the oligodendrocyte is exported to the axon. The oligodendrocyte is probably unable to do its job of myelination and energy support of the axon well because it fails in the glycolysis process.
“Dysfunctional energy metabolism in the brain is not specific to schizophrenia, what we believe is the specific pathway that is glycolysis. This is the pathway that makes us say that the oligodendrocyte is dysfunctional from an energetic point of view”, explained Daniel. The professor adds that glycolysis is a “signature” of schizophrenia.
The advances that the group is achieving come from analyzes from a molecular point of view to identify how proteins act in the establishment of the disease. To achieve this, researchers turn to the proteomic approach, which has allowed large-scale studies of protein expression in different tissues and body fluids. The research findings revealed a list of proteins associated with the energy metabolism of cells, especially oligodendrocytes.
According to the professor, the tissues with the disease come from regions of the brain known to be affected by schizophrenia. “It has been known for at least 20 years that these brain regions were involved, as seen through imaging studies. But there was little biochemical evidence of how proteins act in the disease. This can make us better understand schizophrenia and help us think about new types of treatment.”
Around 30 million people worldwide and 1,7% of the Brazilian population develop the disease, according to the group's researchers. A lot of money is invested to cover patient costs and, despite this, the majority still do not receive adequate treatment. Antipsychotics, although they are the main treatment, have limited action according to researchers, as they were not developed based on the biochemistry of the disease. Patients' personal lives are significantly affected because most are unable to work or study.
The oligodengrocyte is one of the glial cells, which is part of the nervous system. The issue, according to the Unicamp researchers, is that for a long time it was believed that these cells were just a medium, or “glue”, offering almost exclusively physical support for the neurons. “Compared to neurons, little is known about the role of glia in disease. New drugs always seek to treat the neuron, but the findings indicate that the treatment needs to include glial cells,” said Daniel. O laboratory group also investigates how antipsychotics act on oligodendrocytes.
