Antibodies to the protein Immuno-moodulin reduced anxiety of mice

Scientists have found a gene, expression of which are increased in mice prone to autoimmune disorders. The corresponding protein increases anxiety in animals wild type and antibodies to it inhibit anxiety in autoimmune mice. The substance and the gene, called Immuno-moodulin; the authors suggest that the protein may be a marker of mental disorders in autoimmune diseases, and antibodies to it can help with obsessive-compulsive disorder. Article published in the journal Brain, Behavior, and Immunity.

Many people with autoimmune diseases suffer also from mental disorders. For example, about 40 percent of patients with multiple sclerosis trying to commit suicide, about half show a high level of anxiety and depression. Moreover, immunotherapy may worsen mental state. So, reception of interferon beta, which is effective for the treatment of multiple sclerosis, increases the risk of suicidal thoughts. It is not clear how the immune and nervous systems are connected and affect each other and what physiological process underlies the emergence of mental disorders in autoimmune diseases.

Scientists from the UK, Italy and USA under the leadership of Fulvio d’acquisto (Fulvio D’acquisto), University of London, Queen Mary studied the effect on immune T cells annexin A1. This protein is involved in regulation of the immune system and depending on context can trigger both positiveand negative effect, including the activation of T cells. The researchers created a transgenic line of mice in which the expression of annexin A1 in T-cells was increased.

Transgenic animals intensified inflammatory processes. For artificially induced autoimmune diseases (encephalomyelitis and lupus) was significantly more severe compared with the control animals (p < 0.0001). In the affected tissues was increased the content of T-helper cells of type Th1/Th17.

Scientists have noticed that even healthy animals (without autoimmune diseases) in their home cages compulsive digging litter, and some mouse pulled the wool from their neighbors. This behavior resembles obsessive-compulsive disorder person, and the researchers conducted in mice, a number of standard laboratory tests for anxiety, as well as analysis of gene expression in the brain and T-helper cells using DNA microarrays.

Behavioral tests in animals have confirmed the symptoms of anxiety and obsessive-compulsive behavior: they actively hid bulbs in sawdust (p < 0.0001), spent more time in the dark compartment, if the camera consisted of illuminated and dark parts (p < 0.001) and showed reduced vertical mobility (p < 0.01). In the brain of transgenic animals was increased expression of some genes associated with anxiety.

Among the genes whose activity was increased in T-helper cells of transgenic mice, it was a section that encodes a small (about 21 kilodaltons) protein. Scientists have suggested that this is responsible for the connection of anxiety and hyperactivity of the immune system, and called it Immuno-moodulin, or Imood (“mood” is translated to English as the mood and the prefix “immuno” refers to the substances with the immune system). Protein synthesized by recombinant and introduced wild type mice, and antibodies to it — a transgenic animal according annexin A1, and then ran tests on anxiety.

Finally, gene expression Imood evaluated in samples of immune cells of 23 patients with obsessive-compulsive disorder and 20 healthy volunteers.

Mice that were injected Imood, spent significantly less time in the lit compartment of a dark-light chamber, and injection of antibodies to the protein reduced the anxious behavior (p < 0.001). In patients with obsessive-compulsive disorder gene expression Imood was about six times higher than in healthy people (p < 0.0001). The authors suggest that Imood can be a convenient marker of risk for mental disorders in autoimmune diseases, and immunotherapy can be combined with antibodies to the protein, then the improvement of physical health will not be accompanied by symptoms of anxiety.

About autoimmune diseases, history of their discovery, symptoms and causes, read our article “It’s autoimmune”.

Alice Bahareva

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