Neonatal supplementation of oleamide during suckling ameliorates maternal postpartum sleep interruption-induced neural impairment and endocannabinoid dysfunction in early adolescent offspring rats

IntroductionPostpartum sleep disturbances in women are common and can significantly affect maternal mental health and breastfeeding. However, the impact of sleep disruptions in lactating mothers on the neurological and cognitive development of their offspring has not been explored.Materials and meth...

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Main Authors: Linxi Qian, Tao Zheng, Bowen Zhao, Weiye Wang, Yifan Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Nutrition
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Online Access:https://www.frontiersin.org/articles/10.3389/fnut.2025.1566182/full
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author Linxi Qian
Linxi Qian
Tao Zheng
Tao Zheng
Bowen Zhao
Weiye Wang
Yifan Wu
Yifan Wu
author_facet Linxi Qian
Linxi Qian
Tao Zheng
Tao Zheng
Bowen Zhao
Weiye Wang
Yifan Wu
Yifan Wu
author_sort Linxi Qian
collection DOAJ
description IntroductionPostpartum sleep disturbances in women are common and can significantly affect maternal mental health and breastfeeding. However, the impact of sleep disruptions in lactating mothers on the neurological and cognitive development of their offspring has not been explored.Materials and methodsFemale Sprague–Dawley rats were subjected to chronic maternal sleep interruptions (MSI) during lactation. The offspring were divided into four groups: control, MSI, and MSI with low-dose (5 mg/kg·day) or high-dose (25 mg/kg·day) oleamide (ODA) supplementation. Behavioral performance was assessed using the Morris Water Maze (MWM). Neurogenesis and neuroinflammatory markers in the hippocampus were analyzed through immunohistochemistry, Western blotting, and Q-PCR. Levels of endocannabinoids (eCBs) were measured in maternal milk and offspring brain tissues, along with the expression of eCBs-regulating enzymes in offspring brain tissues. NE-4C cells were used to examine the effects of milk from sleep-disrupted dams on neural function.ResultsOffspring exposed to MSI showed increased escape latency, travel distance, and poor performance in the MWM probe test, indicating impaired spatial learning and memory. MSI also decreased neurogenesis markers and increased neuroinflammatory markers in the hippocampus. High-dose ODA supplementation restored behavioral performance, reduced neuroinflammation, and normalized eCBs levels and enzyme expression in the offspring’s hippocampus. Additionally, MSI altered eCBs composition in maternal milk, particularly lowering ODA and 2-AG levels. In vitro, milk from MSI dams inhibited BDNF secretion and reduced anti-inflammatory cytokine expression in NE-4C cells.ConclusionMSI during lactation disrupts eCBs signaling and induces neuroinflammation in the offspring, impairing neurodevelopment. Neonatal ODA supplementation may offer a promising intervention to mitigate the cognitive deficits and brain changes induced by MSI during lactation.
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spelling doaj-art-25e49702bc5d4a07b1a9c5d64c0b33102025-08-20T03:52:47ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2025-05-011210.3389/fnut.2025.15661821566182Neonatal supplementation of oleamide during suckling ameliorates maternal postpartum sleep interruption-induced neural impairment and endocannabinoid dysfunction in early adolescent offspring ratsLinxi Qian0Linxi Qian1Tao Zheng2Tao Zheng3Bowen Zhao4Weiye Wang5Yifan Wu6Yifan Wu7Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaShanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaDepartment of Obstetrics, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaDepartment of Clinical Nutrition, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaMinistry of Education and Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaShanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaIntroductionPostpartum sleep disturbances in women are common and can significantly affect maternal mental health and breastfeeding. However, the impact of sleep disruptions in lactating mothers on the neurological and cognitive development of their offspring has not been explored.Materials and methodsFemale Sprague–Dawley rats were subjected to chronic maternal sleep interruptions (MSI) during lactation. The offspring were divided into four groups: control, MSI, and MSI with low-dose (5 mg/kg·day) or high-dose (25 mg/kg·day) oleamide (ODA) supplementation. Behavioral performance was assessed using the Morris Water Maze (MWM). Neurogenesis and neuroinflammatory markers in the hippocampus were analyzed through immunohistochemistry, Western blotting, and Q-PCR. Levels of endocannabinoids (eCBs) were measured in maternal milk and offspring brain tissues, along with the expression of eCBs-regulating enzymes in offspring brain tissues. NE-4C cells were used to examine the effects of milk from sleep-disrupted dams on neural function.ResultsOffspring exposed to MSI showed increased escape latency, travel distance, and poor performance in the MWM probe test, indicating impaired spatial learning and memory. MSI also decreased neurogenesis markers and increased neuroinflammatory markers in the hippocampus. High-dose ODA supplementation restored behavioral performance, reduced neuroinflammation, and normalized eCBs levels and enzyme expression in the offspring’s hippocampus. Additionally, MSI altered eCBs composition in maternal milk, particularly lowering ODA and 2-AG levels. In vitro, milk from MSI dams inhibited BDNF secretion and reduced anti-inflammatory cytokine expression in NE-4C cells.ConclusionMSI during lactation disrupts eCBs signaling and induces neuroinflammation in the offspring, impairing neurodevelopment. Neonatal ODA supplementation may offer a promising intervention to mitigate the cognitive deficits and brain changes induced by MSI during lactation.https://www.frontiersin.org/articles/10.3389/fnut.2025.1566182/fulloleamidematernal sleep interruptionbreast milkcognitive functionendocannabinoids
spellingShingle Linxi Qian
Linxi Qian
Tao Zheng
Tao Zheng
Bowen Zhao
Weiye Wang
Yifan Wu
Yifan Wu
Neonatal supplementation of oleamide during suckling ameliorates maternal postpartum sleep interruption-induced neural impairment and endocannabinoid dysfunction in early adolescent offspring rats
Frontiers in Nutrition
oleamide
maternal sleep interruption
breast milk
cognitive function
endocannabinoids
title Neonatal supplementation of oleamide during suckling ameliorates maternal postpartum sleep interruption-induced neural impairment and endocannabinoid dysfunction in early adolescent offspring rats
title_full Neonatal supplementation of oleamide during suckling ameliorates maternal postpartum sleep interruption-induced neural impairment and endocannabinoid dysfunction in early adolescent offspring rats
title_fullStr Neonatal supplementation of oleamide during suckling ameliorates maternal postpartum sleep interruption-induced neural impairment and endocannabinoid dysfunction in early adolescent offspring rats
title_full_unstemmed Neonatal supplementation of oleamide during suckling ameliorates maternal postpartum sleep interruption-induced neural impairment and endocannabinoid dysfunction in early adolescent offspring rats
title_short Neonatal supplementation of oleamide during suckling ameliorates maternal postpartum sleep interruption-induced neural impairment and endocannabinoid dysfunction in early adolescent offspring rats
title_sort neonatal supplementation of oleamide during suckling ameliorates maternal postpartum sleep interruption induced neural impairment and endocannabinoid dysfunction in early adolescent offspring rats
topic oleamide
maternal sleep interruption
breast milk
cognitive function
endocannabinoids
url https://www.frontiersin.org/articles/10.3389/fnut.2025.1566182/full
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