Further link identified between autoimmunity and schizophrenia

Date:
May 31, 2023
Source:
Tokyo Medical and Dental University
Summary:
Links have been reported between schizophrenia and proteins produced
by the immune system that can act against one's own body, known
as autoantibodies. Researchers have now identified autoantibodies
that target a 'synaptic adhesion protein' in a subset of patients
with schizophrenia. When injected into mice, the autoantibodies
caused many schizophrenia-related changes.


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FULL STORY ========================================================================== Links have been reported between schizophrenia and proteins produced
by the immune system that can act against one's own body, 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 1a, in a subset of patients with schizophrenia. When injected into mice, the autoantibodies caused many schizophrenia-related changes.

What is a synaptic protein, and why might it be linked to schizophrenia? Synaptic adhesion proteins are specialized proteins that bind to create physical connections between brain cells. These connections, called
synapses, allow the cells to communicate by passing molecules back
and forth. Both synapses and autoimmunity are known to be associated
with schizophrenia, so the research team from Tokyo Medical and Dental University (TMDU) decided to investigate autoantibodies that target
synaptic proteins in patients with schizophrenia.

"In around 2% of our patient population, we identified autoantibodies
against the synaptic protein neurexin 1a, which is expressed by one
cell in the synapse and binds to proteins known as neuroligins on
the other cell in the synapse," says lead author of the study Hiroki
Shiwaku. "Once we had identified these autoantibodies, we wanted to see
if they were able to cause schizophrenia- related changes." To do this,
the researchers isolated autoantibodies from some of the patients with schizophrenia and injected them into the cerebrospinal fluid of mice,
so that the autoantibodies would travel into the brain. In these mice,
the autoantibodies blocked neurexin 1a and neuroligin binding and
altered some related synaptic properties. The administration of these autoantibodies also resulted in fewer synapses in the brains of mice 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 1a can cause schizophrenia-related changes, at least in mice," explains Hiroki Shiwaku. "These autoantibodies may therefore represent
a therapeutic target for a subset of patients with schizophrenia." Schizophrenia has a wide variety of both symptoms and treatment
responses, and many patients have symptoms that are resistant to currently available treatment options. Therefore, the identification of possible disease-causing autoantibodies is important for improving symptom
control in patients with schizophrenia. It is hoped that the results of
this investigation will allow patients with autoantibodies that target
neurexin 1a -- all of whom were resistant to antipsychotic treatment in
the present study -- to better control their symptoms in the future.

* RELATED_TOPICS
o Health_&_Medicine
# Mental_Health_Research # Today's_Healthcare #
HIV_and_AIDS # Diseases_and_Conditions
o Mind_&_Brain
# Schizophrenia # Mental_Health # Disorders_and_Syndromes
# Psychiatry
* RELATED_TERMS
o Schizophrenia o Dopamine_hypothesis_of_schizophrenia o Protein
o Immune_system o Mental_illness o Psychiatric_service_dog o
Psychopathology o Soy_protein

========================================================================== Story Source: Materials provided by
Tokyo_Medical_and_Dental_University. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Hiroki Shiwaku, Shingo Katayama, Mengxuan Gao, Kanoh Kondo,
Yuri Nakano,
Yukiko Motokawa, Saori Toyoda, Fuyuko Yoshida, Hiroaki Hori, Tetsuo
Kubota, Kinya Ishikawa, Hiroshi Kunugi, Yuji Ikegaya, Hitoshi
Okazawa, Hidehiko Takahashi. Analyzing schizophrenia-related
phenotypes in mice caused by autoantibodies against NRXN1a in
schizophrenia. Brain, Behavior, and Immunity, 2023; 111: 32 DOI:
10.1016/j.bbi.2023.03.028 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/05/230531150109.htm

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