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Autoantibodies against NCAM1 cause schizophrenia-related behavior in mice

Autoantibodies against NCAM1 cause schizophrenia-related behavior in mice

“In this new study, investigators demonstrated that “autoantibodies against NCAM1 from schizophrenia patients cause schizophrenia-related behavior and changes in spines and synapses in mice. These autoantibodies may cause symptoms of schizophrenia and can therefore be regarded as a therapeutic target for patients who are positive for anti-NCAM1 autoantibodies.” 1

Anti-NCAM1 autoantibodies in patients with schizophrenia cause schizophrenia-related behavior and changes in synapses in mice.

“The authors concluded, “In this study, we identified anti-NCAM1 autoantibodies in patients with schizophrenia. Administration of IgG antibodies isolated from patients with schizophrenia interrupted NCAM1-NCAM1 and NCAM1-GDNF interactions. These interruptions affect the NCAM1-Fyn-FAK-MEK1-ERK1 signaling pathway and inhibited NCAM1-Fyn interactions as well as the phosphorylation of FAK, MEK1, and ERK1.”

“Furthermore, direct administration of anti-NCAM1 antibodies into the CSF of mice reduced the number of spines and synapses in the frontal cortex and induced cognitive impairment and a deficiency in pre-pulse inhibition, which is an established endophenotype of schizophrenia in humans and mice.”

Study highlights:

  1. Some patients with schizophrenia are positive for anti-NCAM1 autoantibodies
  2. Anti-NCAM1 antibody from schizophrenia patients inhibits NCAM1-NCAM1 interactions
  3. Anti-NCAM1 antibody from schizophrenia patients reduces spines and synapses in mice
  4. Anti-NCAM1 antibody from patients induces schizophrenia-related behavior in mice

How can the Cunningham Panel™ help you in identifying and treating patients with infection-induced autoimmune encephalopathies?

  1. Hiroki Shiwaku, Shingo Katayama, Kanoh Kondo, Yuri Nakano, Hikari Tanaka, Yuki Yoshioka, Kyota Fujita, Haruna Tamaki, Hironao Takebayashi, Omi Terasaki, Yukihiro Nagase, Teruyoshi Nagase, Tetsuo Kubota, Kinya Ishikawa, Hitoshi Okazawa, Hidehiko Takahashi, Autoantibodies against NCAM1 from patients with schizophrenia cause schizophrenia-related behavior and changes in synapses in mice, Cell Reports Medicine, Volume 3, Issue 4, 2022, 100597, ISSN 2666-3791,  https://doi.org/10.1016/j.xcrm.2022.100597.