Neonatal Supplementation of Oleamide During Suckling Promotes Learning Ability and Memory in Adolescent Mice

Abstract

ABSTRACT Background Fatty acid amides (FAMs) are present in breast milk. Oleamide (ODA), a member of the FAM family, has been reported to affect learning and memory-related abilities in animal experiments. Objectives This study aimed to characterize the temporal changes of FAMs in human milk and sought to examine the effect of ODA supplementation during suckling on postweaning cognitive performance in mice. Methods FAMs were measured in human milk (postpartum 1–24 wk) by ultra-performance liquid chromatography-triple quadruple mass spectrometry (UPLC-TQ-MS) analysis. We supplemented neonatal C57BL/6J mice of both sexes with vehicle (control), 5 mg/(kg · day) ODA (L-ODA), or 25 mg/(kg · day) ODA (H-ODA) throughout suckling by oral gavage. After weaning, the Morris water maze test and novel object recognition test were performed. Neurogenesis, spinal morphogenesis in the dentate gyrus (DG) region, and hippocampal expression of synaptic markers were analyzed. Data were analyzed by ANOVA and repeated-measures ANOVA. Results ODA (0.566–1.31 mg/L) was the most abundant FAM in breast milk, followed by palmitamide (0.135–0.269 mg/L) and linoleamide (0.046–0.242 mg/L). Compared with the control group, the H-ODA group demonstrated shorter escape latency, shorter travel distance, 113% more platform crossing, and 48% greater discrimination index in behavioral tests (P < 0.05). Additionally, the H-ODA group showed a higher density of 5-ethynyl-2’-deoxyuridine (EdU)+ and EdU+& doublecortin (DCX)+ cells (62% and 53%, respectively), and 52% greater spine density in the DG region than the control group (P < 0.05). The synaptic markers, postsynaptic density protein 95 (PSD95) and synaptophysin (SYP), were upregulated in the H-ODA group compared with the control group (P < 0.05). The L-ODA group also showed shorter escape latency in behavioral tests and 27% greater spine density in the DG region than the control group (P < 0.05). Conclusions ODA is the most common FAM in human milk. ODA supplementation during suckling promotes learning and memory-related abilities in adolescent mice by augmenting hippocampal neuronal proliferation and boosting synaptic plasticity.