Pharmacology

A group of Brazilian scientists have long conducted experiments with roundworms to investigate the role of schizophrenia-linked genes in patients’ response to antipsychotic drugs. The results obtained thus far point to new ways of understanding resistance to certain classes of medication. The studies are conduct by researchers in the Pharmacology Department of the Federal University of São Paulo’s Medical School (EPM-UNIFESP), collaborating with colleagues at the University of Campinas (UNICAMP).

Pharmacological treatment

An article on some of the findings has been published in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry. Schizophrenia is a highly complex mental disorder with unknown causes and no cure. Pharmacological treatment consists basically of the administration of antipsychotic drugs that control symptoms and help the patient manage social interaction.

First- and second-generation antipsychotics act on the nervous system, mainly by blocking two neurotransmitters, dopamine and serotonin, which play several important roles in the brain. First-generation or typical antipsychotics are dopamine receptor blockers. Second-generation or atypical antipsychotics block both dopamine and serotonin receptors. Some individuals with schizophrenia do not respond to typical antipsychotics and are considere treatment-refractory patients.

Schizophrenic patients

The group’s latest study set out to determine at the molecular level why some patients respond to second-generation but not first-generation antipsychotics. “Schizophrenic patients are known to have lower levels of activity of a specific enzyme called NDEL1 [nuclear distribution element-like 1]. The levels of activity are even lower in treatment-resistant patients;” said Mirian Hayashi, a professor at EPM-UNIFESP and principal investigator for the study.

Hayashi explained that NDEL1 contributes to the degradation of neurotransmitters that play an important role in the brain’s functioning. Because “In our study, They find that NDEL1 may be linked to the development of schizophrenia;” she said. One way to characterize the action of a protein is to use animals that have been genetically modified so as not to express the molecule of interest. These are know as knockout animals.

Caenorhabditis elegans

“We normally use mice or rats as animal models, but in the specific case of our research on NDEL1;  Therefore this isn’t possible. Embryos of rodents that don’t express NDEL1 aren’t viable they don’t develop in utero,” Hayashi said. The alternative is to use an invertebrate; Caenorhabditis elegans, a nematode or roundworm with a length of approximately 1 mm found worldwide in moist soil.
The study described in the article is support by FAPESP – São Paulo Research Foundation. Because The ongoing research is part of the National Institute of Science and Technology in Bioanalysis; which is find by FAPESP and Brazil’s National Council for Scientific and Technological Development