Schizophrenia is a serious disabling mental condition that affects around 23 million individuals worldwide, including 1.5 million Brazilians (PAHO). It is distinguished by out-of-touch ideas or feelings, disordered speech or conduct, and decreased engagement in daily activities. Medication, counseling, and specialist care are used in treatment. To diagnose schizophrenia, a clinical evaluation is necessary.
Research and Study
A study by a group of Brazilian researchers leads to a better understanding of the molecular basis of schizophrenia, potentially paving the path to the development of more precise and effective treatments for the disorder. The medications that are currently available on the market act on the brain in a generic manner and can have serious harmful side effects.
The use of an NMDA receptor (neurotransmitter receptors found in the postsynaptic membrane of neurons that receive signals from previous nerve cells across the synapse) antagonist on post-mortem samples from the hippocampus of schizophrenic patients revealed biological processes linked with the condition that are particular to neurons and oligodendrocytes.
MK-801 was the antagonist in question, a chemical that affects glutamate neurotransmitter function in vitro, simulating what happens in schizophrenia (glutamate being the brain's principal excitatory neurotransmitter). The chemical caused oxidative stress, which is one of the causes that might contribute to brain degeneration, as well as apoptosis in neurons (programmed cell death). Oligodendrocytes, which produce the myelin sheath that protects axons, were not affected in the same way. Oligodendrocytes, on the other hand, showed variations in protein synthesis and myelin membrane structure.
The Laboratory of Neuroproteomics at the University of Campinas' Institute of Biology (UNICAMP) used post-mortem brain tissue samples from schizophrenics.
"After culturing neurons and oligodendrocytes in the lab and treating them with MK-801, we analyzed the proteins in the brain and each cell type, cross-referencing the data. This enabled us to identify differences specific to neurons or oligodendrocytes, or common to both," said Daniel Martins-de-Souza, the study's primary investigator.
Previous research discovered aberrant glutamate levels in schizophrenic patients' brains and related glutamatergic neurotransmission dysfunction to NMDA receptor hypofunction. In humans, glutamatergic neurotransmission is required for thinking, acquisition, and memory.
According to the researchers' article: "The treatment of neural cells with MK-801 revealed that neurons, oligodendrocytes and astrocytes are affected but present different responses to NMDA receptor hypofunction. NMDA receptor activation in oligodendrocytes is involved with their maturation, metabolic modulation and myelination around axons".
The article continues "Thus, understanding the effects of glutamatergic dysregulation in both neurons and oligodendrocytes is crucial to a grasp of the role of these cellular counterparts in schizophrenia, especially in the hippocampal context, we were able to find proteomic signatures in common between the hippocampus and MK-801-treated neurons, and between the hippocampus and the MK-801-treated oligodendrocytes"
These discoveries will aid in the development of therapies that are more specifically tailored to the numerous faulty biological processes in the distinct brain cell types.
