Immune system activity in the central nervous system (CNS) has been implicated in numerous neuroinflammatory diseases. Over the past decade, however, Jonathan Kipnis has found evidence that mice with immune deficiencies also exhibit cognitive impairments.
The CNS houses resident immune cells called microglia. Microglia are extraordinarily dynamic cells, constantly sampling their environment and adjusting to stimuli from early developmental stages throughout the lifespan. Kipnis and his colleagues at the University of Virginia hypothesize that a malfunctioning immune system may underlie some of the behavioral and cognitive impairments seen in children with autism.
Using a mouse model of a severe form of autism called Rett syndrome, Kipnis’ team found in 2012 that microglia play an important role in the disorder. They treated the Rett mice using bone marrow transplantation from wild-type mice. This resulted in the replacement of peripheral immune cells, as well as substantial replacement of brain cells by microglia-like cells from the transplanted bone marrow. Therefore, the immune system, and microglia in particular, can be targeted in Rett syndrome.
Because immune malfunctions are widely studied in autism spectrum disorders and microglia malfunction has also been reported, Kipnis’ team plans to investigate the involvement of microglia in additional models of autism spectrum disorders. This work may provide important preclinical data on the feasibility of microglia-based or microglia-targeted therapies for treating autism spectrum disorders.