1178-P: Interleukin-17 Signaling in Cerebrum of Offspring from Mother with Diabetes

A number of human cohort and animal studies suggest that offspring from mother with diabetes (OMD) has an increased risk of both short- and long-term complications, including various neurological issues including learning impairment and autism spectrum disorders. However, the underlying mechanism of the neurobehavioral issues is still not elucidated. The main objective of this study is to examine their mechanisms by examining gene expression in the cerebrum of OMD during the embryonic period. Six-week-old Crl: CD1 (ICR) females were injected intraperitoneally with 150 mg/kg of STZ for generating OMD. This OMD model showed learning impairment using accelerated rotarod as we previously reported at the 81st Scientific Sessions of the American Diabetes Association. Citrate buffer was used to generate the control group. After mating the females with healthy males, both maternal and fetal cerebrums were collected at embryonic day 17.5. RNA was extracted from the collected cerebrums using TRIzol, and RNA sequencing and quantitative PCR were performed. The number of differentially expressed genes common to three types of analysis (EdgeR, Deseq2, and TCC) was 40. Enrichment analysis of these 40 genes using the KEGG pathway identified a group of genes (Lipocalin-2 (Lcn-2), S100a8, and S100a9) related to the Interleukin 17 (IL-17) pathway. Quantitative PCR revealed mRNA expression of these genes was significantly higher in OMD. In order to investigate the distribution of Lcn-2, we next intraperitoneally administered biotinylated Lcn-2 to pregnant dam at gestational day 17.5 and collect maternal and fetal samples 30 minutes after the administration. Immunohistochemical staining showed that biotin expression was observed in the maternal cortex but not in the fetal one, suggesting that maternally derived Lcn-2 does not reach the fetal cortex. Altogether, our results demonstrate that IL-17 signaling in the fetal brain may be involved in learning impairments in OMD. Disclosure K.Sugai: None. M.Odawara: Speaker's Bureau; Eli Lilly Japan K.K., Novo Nordisk, Sanofi K.K. R.Suzuki: Consultant; Novo Nordisk A/S, Other Relationship; Sanofi K.K., Eli Lilly Japan K.K. J.Sasaki: None. K.Ishii: None. G.Li: None. M.Ito: None. M.Aierken: None. H.Suwanai: None. M.Torii: None. K.Hashimoto-torii: None.