44 - Repeated Exposure to Sucrose and Pain Induces Systemic and Cerebral Alterations in Inflammatory Cytokines in Neonatal Mice

Poster Number: 44
Publication Number: 44.435

Fermin S. Hoq, University of British Columbia Faculty of Medicine, Burnaby, BC, Canada; Rujun Kang, University of British Columbia, Children hospital-Lavoie Lab, Vancouver, BC, Canada; Kiran Soma, UBC, Vancouver, BC, Canada; Annie Ciernia, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Manon Ranger, University of British Columbia, Vancouver, BC, Canada

Background: In the neonatal intensive care unit, preterm infants can experience 7-17 painful and stressful procedures daily. Oral sucrose is the standard treatment for procedural pain, but their combined short- and long-term cumulative effects on brain development remain unclear. Using a neonatal mouse model, we previously showed that repeated sucrose and/or pain exposure in the first week of life resulted in reduced hippocampal and white matter volumes, and poorer short-term memory in adulthood.

Objective: Using our established neonatal mouse model, we aimed to determine whether repeated neonatal sucrose and/or pain exposure during the first week of life affect pro/anti-inflammatory markers in serum and hippocampal tissue of mouse pups.

Design/Methods: Male and female neonatal C57BL/6J mice were randomly assigned to receive orally a micro-drop of water or 24% sucrose prior to handling or needle-prick (pain), 10X/day on postnatal day (P) 1-6. Blood (n=8-15 mice/group) and hippocampal tissue (n=18-24 mice/group) were collected at P8 and assayed for various cytokines (e.g. IL-1β, IL-10, IL-6, and TNF-α). Undisturbed neonatal mice used as controls were also included in our study.

Results: While no sex effects were evident, a significant group effect was found for several pro- and anti-inflammatory cytokines in serum and hippocampal tissue. Mouse pups exposed to sucrose and needle-prick showed significantly lower serum anti-inflammatory IL-5 levels compared to all other groups, including controls. Furthermore, hippocampal anti-inflammatory IL-10 levels were reduced in almost all treatment/intervention groups compared to controls. Preliminary data investigating microglial density in the hippocampus suggests a trend that at P8, male mouse pups exposed to any treatment or intervention exhibit increased microglial density compared to controls.

Conclusion(s): Our findings add to the understanding of possible underlying mechanisms that are driving the adverse effects of sucrose and/or pain on the developing brain. Work is ongoing investigating microglial density in P8 female mice and the longer-term effects on neurodevelopment.