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New evidence for the autoimmune cause of schizophrenia – Neuroscience News

Summary: Researchers have identified autoantibodies that appear to cause schizophrenia in some individuals. The findings add to the growing body of evidence that schizophrenia can have an autoimmune component.

source: Tokyo Medical and Dental University

Schizophrenia is a disorder that affects the way people act, think, and perceive reality. It is often very difficult to treat because there are many different causes and symptoms.

In a study published last month in Medicine Cell ReportsIn some patients with schizophrenia, researchers from Tokyo Medical and Dental University (TMDU) have identified an autoantibody — a protein produced by the immune system to bind to a specific substance from an individual’s own body, rather than a foreign substance such as a virus or bacteria.

Notably, they also found that this antibody induced schizophrenia-like behaviors and changes in the brain when they injected it into mice.

When considering possible autoantibodies that might cause schizophrenia, the research team had a specific protein in mind. Previous research suggested that neuronal cell adhesion molecule1 (NCAM1), which helps cells in the brain talk to each other via specialized connections known as synapses, may have a role in the development of schizophrenia.

“We decided to search for autoantibodies against NCAM1 in approximately 200 healthy controls and 200 patients with schizophrenia,” explains lead study author Hiroki Shiwako.

“We only found these autoantibodies in 12 patients, suggesting that they may be associated with the disorder in only a small subset of schizophrenia cases.”

The research team didn’t stop there — they wanted to see if these autoantibodies could cause any changes that commonly occur in schizophrenia, so they purified the antibodies from some patients and injected them into the brains of mice.

NCAM1 occurs only in green cells (HeLa cells). Serum of patients with anti-NCAM1 autoantibodies only reacts with green cells (framed in red). Credit: Department of Psychiatry and Behavioral Sciences, TMDU

“The results were amazing,” says Hidehiko Takahashi, senior author.

“Although the mice only had these autoantibodies in their brains for a short time, there were changes in their behavior and synapses that were similar to what is seen in humans with schizophrenia.”

Specifically, mice harboring the patient’s autoantibodies had cognitive impairments and alterations in their regulation of startle responses, which have been seen in other animal models of schizophrenia.

They also have fewer synapses and dendritic spines, which are important structures for communication between brain cells, and are also affected by schizophrenia.

Given that schizophrenia can present quite differently between patients and is often treatment-resistant, the results of this study are promising.

If schizophrenia is indeed caused by antibodies against NCAM1 in some patients, this would lead to important improvements in their diagnosis and treatment.

About this research on schizophrenia news

author: Hiroki Shiwaku
source: Tokyo Medical and Dental University
Contact: Hiroki Shiwako – Tokyo Medical and Dental University
picture: The image is attributed to the Department of Psychiatry and Behavioral Sciences, TMDU

original search: open access.
“Autoantibodies against NCAM1 from patients with schizophrenia cause schizophrenia-related behavior and synaptic changes in mice” by Hidehiko Takahashi et al. Medicine Cell Reports

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Summary

Autoantibodies against NCAM1 from patients with schizophrenia cause schizophrenia-related behavior and synaptic changes in mice.

Highlights

  • Some patients with schizophrenia have anti-NCAM1 autoantibodies
  • Anti-NCAM1 antibodies from patients with schizophrenia inhibit NCAM1-NCAM1 . interactions
  • The anti-NCAM1 antibody reduces schizophrenia and spine and synapses in mice
  • Anti-NCAM1 antibodies from patients induce schizophrenia-related behavior in mice

Summary

From genetic and etiological studies, autoimmune mechanisms underlying schizophrenia are suspected; However, the details are still unclear.

In this study, we described autoantibodies against neuronal cell adhesion molecule1 (NCAM1) in patients with schizophrenia (5.4%, cell-based assay; 6.7%, ELISA) in a Japanese group (n = 223). The anti-NCAM1 autoantibody disrupts the interactions of glial cell line NCAM1-NCAM1- and NCAM1-derived neurotrophic factor.

Moreover, anti-NCAM1 antibody purified from schizophrenic patients interrupts the NCAM1-Fyn interaction and blocks the phosphorylation of FAK, MEK1 and ERK1 when introduced into the cerebrospinal fluid of mice and also reduces the number of spines and synapses in the frontal cortex.

In addition, it stimulates behavior associated with schizophrenia in mice, including impaired prior impulse inhibition and cognitive impairment. In conclusion, anti-NCAM1 autoantibodies in schizophrenic patients induced schizophrenia-related behavior and changes in synapses in mice.

These antibodies may be a potential therapeutic target and serve as a biomarker to distinguish a small but treatable subgroup in heterogeneous schizophrenia patients.

2022-06-06 17:13:05

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