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

Ranran Tao; Shanshan Huang; Jiefei Zhou; Lin Ye; Xiuhua Shen; Jiang Wu; Linxi Qian

doi:10.1093/jn/nxab442

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

J Nutr. 2022 Mar 3;152(3):889-898. doi: 10.1093/jn/nxab442.

Authors

Ranran Tao^{1

2}, Shanshan Huang^{1

2}, Jiefei Zhou^{1

2}, Lin Ye^{1

2}, Xiuhua Shen³, Jiang Wu⁴, Linxi Qian^{1

2}

Affiliations

¹ Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
³ Department of Nutrition, School of Public Health, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Nutrition, Huadong Hospital Affiliated to Fudan University, Shanghai, China.

PMID: 34967906
DOI: 10.1093/jn/nxab442

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.

Keywords: breast milk; cognitive function; fatty acid amides; hippocampal neurogenesis; oleamide; synaptic plasticity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Dietary Supplements
Disks Large Homolog 4 Protein / metabolism
Female
Hippocampus* / metabolism
Humans
Male
Maze Learning
Mice
Mice, Inbred C57BL
Neurogenesis*
Oleic Acids

Substances

Disks Large Homolog 4 Protein
Oleic Acids
oleylamide