Japanese scientists have discovered that the corpus callosum of patients with schizophrenia reduced the concentration of sphingosine-1-phosphate — one of the key elements of lipid metabolism in the brain. This was indicated by postmortem analysis of brain tissue in patients, with a similar dynamics was observed in healthy people and in patients with bipolar disorder and depression. The reduced concentration was associated not with a lack of production, and with the rapid destruction of the receptors to sphingosine-1-phosphate may be a target for the treatment of schizophrenia in the future, write the scientists in Schizophrenia Bulletin.
Despite the fact that schizophrenia is quite well studied disease (both symptomatically and in terms of pathophysiology), its causes and neurobiologically the exact mechanism still remains unknown. This is when some markers still manage to allocate: for example, early in the year, scientists foundthat people with schizophrenia in some parts of the brain below the concentration of protein SV2A — he is involved in the formation of synaptic connections.
Another well-known symptom of schizophrenia — disorders of the structure of the white matter and the lack of it in the brain, but the biological basis of such changes, very little is known. It is assumed that the cause may be disruption of oligodendrocytes and the formation by them of the myelin sheath of neurons. These processes, in turn, is almost entirely tied to lipid metabolism in the fats and their derivatives, therefore, may lie the basis of the mechanism of disruption of white matter.
Check it decided scientists under the leadership Yoshikawa Takeo (Takeo Yoshikawa) from the research Center for brain science RIKEN enterprises. They focused on the sphingolipids , one of the main groups of substances involved in lipid metabolism in the brain and responsible for the normalization of its work.
Using mass spectrometry, the researchers assessed the concentration of sphingolipids in the corpus callosum (the largest concentration of the white matter of the brain) and one of the areas of the cortex — premotor area. Analysis took place post mortem: scientists collected samples of the brain of 15 patients with schizophrenia, 15 patients with bipolar disorder, 15 depression and 15 healthy people.
The analysis showed that the corpus callosum of patients with schizophrenia, in contrast to the control group, 31 per cent below the concentration signal sphingolipid sphingosine-1-phosphate. Its concentration in the brain of other patients with depression and bipolar disorder — did not differ significantly from the control group.
Concentration sphingosine-1-phosphate in the brain of patients is also not depended on whether they took during the life of antipsychotic drugs for relief of symptoms (p = 0,054). To clarify, the researchers also analyzed brain tissue of mice for four weeks before euthanasia took either haloperidol or risperidone or saline (the control group). In mice, the scientists also podtverdili that the exchange of sphingolipids in the brain is not regulated by antipsychotic drugs.
Next, the researchers examined gene expression in brain tissues of mice and patients. They found increased expression of the gene SGPL1, which encodes the major in its production enzyme — sphingosine-1-phosphate-lyase, on the one hand, and increased expression of PLPP3that encodes the destructive enzyme — phospholipid-phosphatase-3. Both of these gene are involved in the metabolism of sphingosine-1-phosphate, but the expression of PLPP3 was five times higher: this means that sphingosine-1-phosphate, most likely, produced in normal amount, but actively destroyed, which leads to its low concentration.
The authors concluded that in the treatment of schizophrenia can be useful for drugs that affect the receptor sphingosine-1-phosphate. This can be a real treatment of the disease, not eliminate the symptoms, as this substance is not amenable to antipsychotic drugs.
Schizophrenia is a heritable disease, but responsible for its development genes still have not been fully defined. Last year, however, scientists have been able to limit the genotype of the disease 413 genes.