20644
Increased Proinflammatory Cytokines Associated with Increased Abnormal Behaviors in a Non-Human Primate Model of Maternal Immune Activation
Objectives: To further investigate behavioral and immune abnormalities in a non human primate model of maternal immune activation.
Methods: Twenty-one pregnant rhesus macaques were placed into four treatment groups: first trimester poly IC, first trimester Saline, second trimester poly IC and second trimester saline. Animals were given three injections over the course of 72 hours with either poly IC, a double stranded RNA analog, used to induce an immune response in the absence of an infection or saline as a control. Injections were given either near the end of the first trimester or near the end of the second trimester depending on the treatment group of the animal. Over the next four years offspring from the treatment animals underwent several behavioral analysis and had blood collected at the end of their second and forth years. Plasma cytokine levels and supernatants from stimulated peripheral blood mononuclear cells (PBMC) were measured using a multiplex assay.
Results: Animals injected with poly IC had offspring who demonstrated increased stereotyped behaviors. In addition to these differences in behaviors offspring also showed persistent elevated production of inflammatory cytokines under multiple conditions including: G-CSF, IL-1β, IL-2, IL-4, IL-8, IL-12p40 and MCP-1. Many of these cytokines positively correlated with increased self directed behavior including G-CSF, IL-1β, IL-4 and IL-12p40 while IL-1β and IL-8 negatively correlated with whole body stereotyped behaviors.
Conclusions: MIA increases the risk for offspring to exhibit an altered behavior phenotype. In addition, MIA affects the immune profile of the offspring. Neuro-immune interactions are increasingly associated with neurodevelopmental disorders. By further studying these interactions we can better our understanding of how these two systems work together in typical development and in neurodevelopmental disorders.