Immunity as a regulator of social behavior
Dronk.Ru, Geektimes, based on University of Virginia: Shocking New Role Found for the Immune System: Controlling Social Interactions
According to the results of recent joint experiments conducted by researchers from the laboratory of the University of Virginia and Massachusetts, the immune system is directly involved in the regulation of neural connections and social behavior. A detailed report on the work done and the conclusions of the scientists are published on the pages of the journal Nature (Filiano et al., Unexpected role of interferon-γ in regulating neuronal connectivity and social behavior).
In their work, the specialists used mice with congenital severe combined immunodeficiency (damage to the acquired immunity system). In the standard three-chamber socialization test, such animals, unlike healthy ones, were interested in their relatives to the same extent as inanimate objects surrounding them. At the same time, the mice showed practically no manifestations of anxiety, motor or olfactory deficits.
fMRI conducted at rest revealed in immunodeficient mice a sharply increased number of neural connections between multiple areas of the frontal cortex and insular gyrus responsible for social behavior. A very similar pattern is observed in animals with simulated social disorders and people with autism spectrum disorders.
At the age of four weeks, mice with immunodeficiency were injected with normal T-lymphocytes. After another four weeks, such animals in the "socialization" test did not differ from healthy ones. Neural connections have also normalized in the corresponding parts of the brain.
The introduction of antibodies to integrin VLA4 to healthy animals, which prevent the penetration of T-lymphocytes into the meninges, on the contrary, caused them "socialization" disorders similar to the behavior of immunodeficient mice.
To find out which signaling pathways dependent on T-lymphocytes (interferon-gamma, interleukins 4/13, 17 and 10, transforming growth factor beta) determine social behavior, scientists analyzed the representation of functional groups of genes (GSEA) in 41 transcriptomes of the cerebral cortex of rats and mice after the action of various stimulating factors, including social aggregation, sleep deprivation, stress, the introduction of psychostimulants, antidepressants, anticonvulsants and antipsychotic drugs. As it turned out, during social aggregation and the use of psychostimulants, the expression of genes regulated by interferon-gamma increases.
The relationship of cytokine expression with various stimuli.
Here and below are the drawings from the article in Nature.
In the course of further experiments, it turned out that mice with a deficiency of this immunity mediator have the same social disorders and disorders of neural connections as mice with immunodeficiency. The introduction of interferon-gamma into the cerebrospinal fluid made it possible to eliminate these disorders. In the course of research, scientists also managed to find out that neurons of the prefrontal cortex express receptors for interferon-gamma, and suppression of this expression leads to social behavior disorders.
Experiments with freshly prepared samples of neurons have shown that interferon-gamma suppresses the activity of neurons by increasing the level of the inhibitory neurotransmitter GABA. This means that socialization disorders in immunodeficiency are the result of excessive activation of prefrontal cortex cells.
Considering that interferon-gamma is one of the most important mediators of the immune response, scientists have suggested that such a double effect was the result of an evolutionary need to increase immunity when relatives appear in society, where pathogens are intensively spreading. To test the hypothesis, the researchers analyzed publicly available transcriptomes of representatives of various species, including rats, mice, zebrafish and fruit flies. GSEA showed that in all these animals, being in a close community activates immune mechanisms even in the absence of infections, and isolation, on the contrary, leads to their suppression.
The relationship between socialization and cytokine expression in
mice, rats, danio-rerio fish and fruit flies.
Thus, the experiments carried out and the results obtained allowed us to draw an amazing conclusion: the immune system is an important regulator of social behavior, and a number of behavioral traits could well have appeared in the process of evolution, as a consequence of the fight of immunity against infections. "It sounds crazy, but perhaps we are just multicellular battlefields of two ancient forces: pathogens and the immune system. Part of our personality may actually be under the control of immunity," explained the head of the work Jonathan Kipnis (Jonathan Kipnis).
The results obtained can significantly influence the understanding of the causes of autism spectrum disorders and schizophrenia, as well as the search for new ways and approaches to the treatment of these conditions.
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19.07.2016