MSGID: 1:317/3 64781f04   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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   
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   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   
      
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   Story Source: Materials provided by   
   Tokyo_Medical_and_Dental_University. Note: Content may be edited for   
   style and length.   
      
      
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   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   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/05/230531150109.htm   
      
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