251 - Intranasal Insulin Treatment Alters Gene Expression Profile in the Hippocampus of Rats with Perinatal Iron Deficiency

Poster Number: 251
Publication Number: 251.141

Brian Sandri, University of Minnesota Medical School, Minneapolis, MN, United States; Kathleen Ennis-Czerniak, University of Minnesota, Minneapolis, MN, United States; Priya Kanajam, University of Minnesota, Maple Grove, MN, United States; Alexandra Burt, University of Minnesota- Twin Cities, Woodbury, MN, United States; Michael K. Georgieff, University of Minnesota, Minneapolis, MN, United States; Raghavendra Rao, University of Minnesota Medical School, Minneapolis, MN, United States

Background: Perinatal iron deficiency (ID) targets the hippocampus and leads to long-term cognitive deficits. Such deficits remain after iron repletion suggesting that further insight into the mechanisms of cognitive deficits and adjunct treatments are needed. Intranasal insulin improves cognitive deficits in Alzheimer’s disease and type 2 diabetes.

Objective: Assess the effects of intranasal insulin administration on the hippocampal transcriptome in rat model of perinatal ID.

Design/Methods: Perinatal ID was induced using a low iron diet during gestation and until postnatal day (P) 7, followed by iron sufficient (IS) diet until P21. Intranasal insulin was administered at a dose of 0.3 IU, twice daily from P8 to P20. Hippocampi were removed on P21 from IS control, ID control, IS insulin, and ID insulin groups. Total RNA was isolated and profiled using TruSeq next-generation sequencing (Illumina). Gene expression profiles were characterized using custom Galaxy workflows and expression patterns examined using Ingenuity Pathways (Qiagen) n=7-9 per group.

Results: At P8, prior to insulin treatment, the IS group hematocrit levels averaged 28.0±2.1 with the ID group averaging 13.8±2.3. The hematocrit values at P21, prior to harvest, for IS control was 33.4%±1.2, 31.3%±1.1 with insulin treatment, ID groups averaged 27.2%±3.4 for controls and 26.7%±2.3 with insulin treatment. Transcriptomic profiling revealed that mitochondrial biogenesis and flux, oxidative phosphorylation, quantity of neurons, CREB signaling in neurons, and RICTOR-based mTOR signaling were disrupted with ID and positively affected by insulin treatment with the most benefit generally observed in the ID insulin-treated group.Conclusion(s): Both perinatal ID and insulin administration alter gene expression in the developing hippocampus. Intranasal insulin treatment reversed the adverse effects of ID on many molecular pathways and should be further explored.