A non-human primate autism model based on maternal infection

  • Awarded: 2007
  • Award Type: Research
  • Award #: SFARI-07-30

Viral infection during pregnancy raises the risk of autism in the offspring, suggesting a connection between the maternal immune system and fetal brain development. Paul Patterson of the California Institute of Technology and his colleagues have successfully modeled this scenario in mice. In collaboration with David Amaral’s group at the University of California, Davis, they plan to extend these studies to non-human primates, which are socially and physiologically more similar to humans.

Viral infections activate the immune system, causing inflammation and other defensive responses throughout the body. The immune activation is critical for the mother to fight infection, but mouse studies have shown that this also results in immune activation in the placenta and the fetus. It is possible that these immune responses may remain active in the offspring, which could be linked to the abnormally high frequency of inflammation in the brains of people with autism.

To study this phenomenon, Patterson and his team induced an immune response to viral infection in pregnant mice, and found that the offspring have several characteristics of autism. The mice display a series of behavioral abnormalities, including elevated anxiety and few social interactions. They also have fewer Purkinje neurons in the cerebellum, mimicking a pathology seen in the brains of people with autism. Although mice are social animals, their behaviors and communication methods are difficult to compare directly with human behaviors.

Patterson and Amaral therefore plan to extend this model to rhesus monkeys. The social behaviors of rhesus monkeys have been thoroughly cataloged, allowing researchers to detect subtle differences in the ways the animals interact with each other and with their mothers. For example, the monkeys may not be able to interpret facial expressions or may have difficulty communicating, as people with autism do. The researchers plan to perform post-mortem autopsies to look for the neurological causes of the observed behaviors, in particular inflammation and neuronal damage. These studies could have important implications for the diagnosis and treatment of autism.

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