A complex and mysterious mental disorder may be associated with an “attack of the body on the brain” — with antibodies attacking the body’s own proteins.
Scientists from the Tokyo University of Medicine and Dentistry (TMDU) have found autoantibodies in some patients with schizophrenia — immune proteins that interact with proteins of their own body instead of virus or bacterial antigens. These antibodies attack the NCAM1 protein, which provides interaction between brain neurons. Being isolated from such people and introduced into the body of experimental mice, they caused symptoms similar to schizophrenia in animals. Biologists write about this in an article published in the journal Cell Reports Medicine.
Schizophrenia is a mental disorder with very diverse symptoms, sometimes reaching a deep breakdown of personality and emotional sphere, hallucinations and paranoia. At different periods of life, it can develop in 0.5-1% of the population, but the cause of schizophrenia remains unclear. Various hypotheses associate it with heredity, disorders of early development or the exchange of neurotransmitters in the brain, with some somatic diseases, including autoimmune. The latter option was also indicated by a new work conducted by Hiroki Shiwaku and his colleagues.
The protein NCAM1 (Neural cell adhesion molecule 1 — neural molecule of intercellular adhesion 1) plays an important role in the intercellular interactions of neurons and their supporting glia, in muscles and some blood cells. It ensures the formation and consolidation of synapses, in which signals are exchanged between neurons. Many past studies have shown that violations of the synthesis or functionality of NCAM1 are often found in patients with schizophrenia. And switching off the NCAM1 gene in laboratory mice leads to the development of corresponding symptoms in them.
Hiroki Shivaku and his co-authors examined about 200 people suffering from schizophrenia, and the same number without such a diagnosis. Autoantibodies binding NCAM1 (anti-NCAM1) were isolated in 12 patients. This may indicate that, at least in some cases, the development of the disorder is caused by autoimmune processes that disrupt interactions between neurons and the formation of synapses. Indeed, experiments conducted “in vitro” with cultures of neurons and glial cells (which play an auxiliary function in the nervous system) have shown that the addition of purified anti-NCAM1 proteins disrupts their “communication” with each other.
The same was indicated by experiments with laboratory mice in which the anti-NCAM1 drug was injected into the cerebrospinal fluid. Such animals soon developed cognitive impairments, the start reflex weakened (alertness in response to a sharp external stimulus), they showed other signs characteristic of animal models of schizophrenia. Neurons of mice treated with anti-NCAM1 formed fewer synapses and dendritic spikes on which synapses can form.
Perhaps the work will finally allow us to find effective medications for the treatment of schizophrenia. At least, for those patients in whom the disease really has an autoimmune nature.