Autoantibodies against synaptic protein neurexin 1α strongly linked to schizophrenia, study shows
A recent study conducted by Japanese researchers has identified a strong link between schizophrenia and autoantibodies that target a synaptic adhesion protein in a subset of schizophrenia patients. The study, published in Brain, Behavior, and Immunity journal last month, suggests that these autoantibodies against synaptic protein neurexin 1α can trigger schizophrenia-related changes in the brain.
What are synaptic proteins and how might they be related to schizophrenia?
Synaptic adhesion proteins are specialized proteins that bring together brain cells to create physical connections known as synapses. Both synapses and autoimmunity are associated with schizophrenia. The Tokyo Medical and Dental University (TMDU) research team decided to investigate autoantibodies targeting synaptic proteins in patients with schizophrenia. The research identified autoantibodies against the synaptic protein neurexin 1α in about 2% of the patient population.
What did the study discover?
To test the effects of these autoantibodies, the researchers injected them into the cerebrospinal fluid of mice, allowing the autoantibodies to travel to the brain. The autoantibodies blocked the binding of neurexin 1α and neuroligin, causing some synaptic properties alterations in the mice’s brains. Moreover, administering these autoantibodies resulted in fewer synapses in the mice’s brains and schizophrenia-like behaviors such as reduced social behavior towards unfamiliar mice and reduced cognitive function. These autoantibodies may represent a potential therapeutic target for a subset of patients with schizophrenia.
What can this study mean for the future?
Since schizophrenia features diverse symptoms and treatment responses, identification of potential disease-causing autoantibodies is necessary to better control symptoms in schizophrenia patients. The results of this investigation offer possibilities for improved symptom control in patients with autoantibodies targeting neurexin 1α who are resistant to antipsychotic treatment. The research suggests that this can be used as a therapeutic target for treating a subset of patients with schizophrenia.
Additional Piece:
Researchers have been looking into ways of treating schizophrenia, a mental health disorder that affects millions worldwide. One of the major challenges to treating this condition is its complexity. This research implies that autoantibodies against neuropsychiatric disorders could also play a role in causing psychiatric, autoimmune, or neurologic disorders affecting the nervous systems. Clarifying the relationship between schizophrenia and autoantibodies could pave the way for more precise treatments.
The study also paves the way for developing a new class of medications that could aim to block these antibodies from binding to their target. It could offer hope to thousands of individuals with schizophrenia resistant to antipsychotic treatment.
Furthermore, the discovery implies a need to re-examine current diagnostic protocols. In certain cases, it could prove to be a significant finding where the diagnosis is solely based on schizophrenia symptoms and not an underlying biochemical process. It could also indicate that there is no need to change the diagnosis, but stratifying patients based on their disease-specific biomarkers could be an option.
In conclusion, the study has opened up a new avenue in understanding the mechanisms behind schizophrenia. Clinicians and scientists will continue to dig deep into autoantibodies, signaling pathways, and mechanisms of abnormal electrical activity, opening up possibilities for new therapeutic and diagnostic strategies for people with schizophrenia. With the findings from this study, we have a better understanding of schizophrenia and what treatments may work and what could be the future possibilities in treating the illness.
Summary:
Autoantibodies are proteins produced by the immune system that can act against the body itself. A recent study by Japanese researchers has found that autoantibodies targeted at synaptic adhesion protein neurexin 1α in a subset of schizophrenia patients can trigger schizophrenia-associated changes in the brain. The findings offer potential therapeutic targets for patients resistant to antipsychotic treatment. The study also implies a need to re-examine current diagnostic protocols. With the findings from this study, we have a better understanding of schizophrenia and what treatments may work and what could be the future possibilities in treating the illness.
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Links have been reported between schizophrenia and proteins produced by the immune system that can act against the body itself, known as autoantibodies. In a study published last month in Brain behavior and immunity, Japanese researchers identified autoantibodies that target a “synaptic adhesion protein,” neurexin 1α, in a subset of patients with schizophrenia. When injected into mice, the autoantibodies caused many changes associated with schizophrenia.
What is a synaptic protein and why might it be related to schizophrenia? Synaptic adhesion proteins are specialized proteins that come together to create physical connections between brain cells. These connections, called synapses, allow cells to communicate by passing molecules back and forth. Both synapses and autoimmunity are known to be associated with schizophrenia, so the research team at Tokyo Medical and Dental University (TMDU) decided to investigate autoantibodies targeting synaptic proteins in patients with schizophrenia.
“In about 2% of our patient population, we identified autoantibodies against the synaptic protein neurexin 1α, which is expressed on one cell of the synapse and binds to proteins known as neuroligins on the other cell of the synapse,” says the author. study principal. study Hiroki Shiwaku. “Once we identified these autoantibodies, we wanted to see if they could cause schizophrenia-related changes.”
To do this, the researchers isolated autoantibodies from some of the schizophrenia patients and injected them into the cerebrospinal fluid of mice, so that the autoantibodies traveled to the brain. In these mice, the autoantibodies blocked the binding of neurexin 1α and neuroligin and altered some related synaptic properties. Administration of these autoantibodies also resulted in fewer synapses in the mice’s brains and schizophrenia-related behaviors, such as reduced social behavior toward unfamiliar mice and reduced cognitive function.
“Together, our results strongly suggest that autoantibodies against neurexin 1α can cause schizophrenia-related changes, at least in mice,” explains Hiroki Shiwaku. “These autoantibodies, therefore, may represent a therapeutic target for a subset of patients with schizophrenia.”
Schizophrenia has a wide variety of symptoms and responses to treatment, and many patients have symptoms that are resistant to currently available treatment options. Therefore, identification of potential disease-causing autoantibodies is important to improve symptom control in patients with schizophrenia. The results of this investigation are expected to enable patients with autoantibodies targeting neurexin 1α, all of whom were resistant to antipsychotic treatment in the present study, to better control their symptoms in the future.
https://www.sciencedaily.com/releases/2023/05/230531150109.htm
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