If the immune system attacks your body, it can often have devastating consequences: autoantibodies bind to the structures of the body, triggering functional disorders. Glutamate receptors, a neurotransmitter, can also become the target of autoantibodies. Researchers from the Max Planck Institute of Experimental Medicine in Göttingen investigated the circumstances under which autoantibodies are formed for a particular glutamate receptor – known as the NMDA receptor – and their effects in the brain. The researchers found that the level of these autoantibodies in the blood can vary greatly over a person’s life – regardless of health conditions – and increases with age. Chronic stress can, however, increase the concentration of these autoantibodies in the blood even in the early years of life. According to the researchers, when antibodies are able to enter the brain to act on NMDA receptors, people suffer from less depression and anxiety. These autoantibodies clearly act as the body’s antidepressants.
Glutamate receptors are located in the membrane of nerve cells and bind to glutamate, a neurotransmitter. The NMDA receptor is a type of receptor essential for learning and memory. Up to 20 percent of the population has antibodies to this receptor in the blood.
Usually, the blood-brain barrier prevents these antibodies from passing through the blood to the brain. Only if this barrier is damaged can the antibodies have a greater effect. If antibodies bind to NMDA receptors in the brain, they are removed from the nerve cell membrane (“internalized”). This stops reporting to nearby cells. If inflammation is present in the brain, for example due to a viral infection, the presence of these autoantibodies can lead to a so-called “anti-NMDAR encephalitis”: a disease brought to the attention of the public from the 2016 movie “Brain on Fire “. The effect of these NMDA receptor autoantibodies can typically influence the symptoms of the underlying encephalitis, contributing to epileptic seizures, impaired movement, psychosis and loss of cognitive function.
Autoantibody levels increase with age
In a new study, Hannelore Ehrenreich and his colleagues at the Max Planck Institute for Experimental Medicine in Göttingen found that the concentration of these autoantibodies in the blood of mice and humans can fluctuate considerably over time. However, the level increases with age, as the body is continuously exposed to factors that stimulate the immune system and, with it, the production of autoantibodies. One of these factors is stress. According to the researchers, chronically stressed mice show a higher level of NMDA receptor autoantibodies in the blood than their non-stressed components.
Ehrenreich and his team also analyzed the concentration of antibodies in the blood of young migrants. “People who are subjected to severe stress in their lives are more likely to carry NMDA receptor autoantibodies in the blood, even at a young age,” says Ehrenreich. These are like a time bomb in the body. “If an infection or some other factor appears that weakens the blood brain barrier, autoantibodies enter the brain and can cause epileptic seizures or other neurological disorders,” says Ehrenreich. A good example would be Knut, Berlin’s famous polar bear.
Positive effect of antibodies
However, the researchers’ recent study indicated for the first time that autoantibodies can also play a positive role in the brain. Mice with a more permeable blood-brain barrier and NMDA receptor autoantibodies in the brain were significantly more mobile and less depressed during periods of chronic stress than their conspecifics with an intact blood-brain barrier. An analysis of a large patient database revealed that people with NMDA autoantibodies and a permeable blood brain barrier also suffered significantly less depression and anxiety.
The autoantibody NMDA obviously has a role in the brain similar to ketamine, an antidepressant that also acts on NMDA receptors.
The effect of these autoantibodies – which contribute to the symptoms of an encephalitis or inhibit depression – is evidently determined not only by their level in the brain, but also by any underlying conditions, in particular the presence or absence of inflammation “.
Hannelore Ehrenreich, Max Planck Institute of Experimental Medicine