121. Early postnatal respiratory viral infection alters hippocampal neurogenesis, cell fate, and neuron morphology in the neonatal piglet

Abstract

Respiratory infections are common during the neonatal period in humans, but little is known about their impact on brain development. The current study used a neonatal piglet model with porcine reproductive and respiratory syndrome virus (PRRSV) to assess how respiratory infection affects hippocampal neurogenesis and neuron morphology. Piglets received one bromodeoxyuridine (BrdU) injection on postnatal day (PD) 7 and then were inoculated with PRRSV. BrdU+ cells and cell fate were quantified in the dentate gyrus on PD28. PRRSV induced fever and sickness behavior throughout the study, and plasma TNF α was still elevated in PRRSV piglets at PD28. New cell survival was affected by sex, with males having more BrdU+ cells than females. Furthermore, a sex × treatment interaction indicated PRRSV decreased BrdU+ cells in males only. Remarkably, both male and female PRRSV piglets showed a 24% reduction in neurogenesis. About 15% of newly divided cells formed microglia in males and females, but this was not affected by PRRSV. Dentate granule cell morphology was determined by Golgi staining and Sholl analysis. PRRSV affected the inner granule cell morphology such that the first branch point was extended further from the cell body. Males had more complex dendrites than females in the outer granule cell layer, but this was not affected by PRRSV. These findings suggest that early-life infection can impact brain development. Supported by HD069899.