Poster Topical Area: Neurobiology
Location: Hall D
Poster Board Number: 719
Objective. This study investigated negative impacts on neurodevelopment and neuroinflammation caused by concurrent postnatal iron deficiency (ID) and respiratory infection using a neonatal piglet model. We hypothesized that ID would reduce immune activation and cytokine expression, reduce expression of genes associated with neurodevelopment, and impair monoamine metabolism.
Methods. On postnatal day 2 (PD 2) piglets were divided into four groups (N = 30), and fed either iron normal (N) or ID sow milk replacer. Piglets were inoculated with either vehicle (C) or porcine reproductive and respiratory syndrome virus (PRRSV) on PD 8. Rectal temperatures, feeding score and sickness behaviors were measured daily until piglets were harvested on PD 28. Tissues were collected to measure monoamine levels, cell isolation, and gene expression.
Results. Hematocrit, hemoglobin, and serum iron were reduced by ID (p < 0.0001) but not PRRSV infection. PRRSV-infected piglets displayed viremia on PD 14, though ID-PRRSV viremia remained consistent while N-PRRSV piglets had reduced viremia PD 28 (p = 0.0074). Expression of iron metabolism, cytokine, and anti-microbial genes in the brain and periphery was altered differentially across tissues by an interaction between diet and infection, as well as separate main effects. Brain weight was reduced by PRRSV infection but not ID (p = 0.01). Microglial activation was increased by infection (p < 0.0001) but unaffected by ID, as was microglial cytokine expression, though hippocampal TNFα expression was increased by infection and heightened by an interaction with ID. Expression of hippocampal genes involved with neurodevelopment and energy metabolism was disrupted by interactions between ID and infection, a pattern observed in the striatum and amygdala as well. Dopamine metabolism was profoundly altered in key brain regions including the hippocampus, medial prefrontal cortex, striatum and amygdala due to ID, infection, and interaction of ID with PRRSV infection.
Conclusions. ID altered cytokine expression, reduced anti-microbial gene expression, and impaired viral clearance. Altered neurodevelopmental gene expression in the hippocampus may contribute to impaired learning and memory observed in postnatally ID animals. Altered dopamine metabolism in the medial prefrontal cortex and amygdala may contribute to increased fear, anxiety and reduced stress resilience reported with postnatal ID and infection.
University of Illinois at Urbana–Champaign