28. Early-life viral infection causes neuroinflammation, cognitive deficits, and changes in neurogenesis in the neonatal piglet

Abstract

Environmental insults during sensitive developmental periods can affect neural cells and circuits, slow cognitive development, and increase the risk for behavioral disorders. However, the ramifications of postnatal infection on brain and cognitive development are poorly understood. Using a neonatal piglet model, we showed that infection with the porcine reproductive and respiratory syndrome virus (PRRSV), a model of viral pneumonia, caused drastic microglial cell activation within the hippocampus with 82% and 43% of microglia being MHC-II positive at 13 and 20 days post-inoculation, respectively. In control piglets, less than 5% of microglia in the hippocampus were MHC-II positive. Increased inflammatory gene expression (e.g., IL-1B, IL-6, TNFa, and IFNY) was seen across multiple brain regions including the hippocampus. In a hippocampal-dependent spatial t-maze task, PRRSV piglets took longer to acquire the task, had a longer latency to choice, and a higher total distance moved. PRRSV also affected neurogenesis in the piglet dentate gyrus. In non-infected controls there were more BrdU-positive cells in males than females. PRRSV caused a reduction in surviving cells in males, but there were no changes in females. In addition, there was a ∼30% reduction in the number of new cells that developed into mature neurons in both males and females with PRRSV. These data suggest that early-life neuroinflammation has a profound effect on brain and cognitive development.