Yonatan Eden, Shukha Orya Noa, Golani Idit, Abu-Ata Saher, Awad-Igbaria Yaseen, Khatib Nizar, Ginsberg Yuval, Palzur Eilam, Beloosesky Ron, Shamir Alon
Psychobiology Research Laboratory, Mazor Mental Health Center, Akko, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Department of Biotechnology Engineering, Braude College of Engineering, Karmiel, Israel.
Neuropharmacology. 2025 Jun 15;271:110390. doi: 10.1016/j.neuropharm.2025.110390. Epub 2025 Feb 27.
Maternal obesity in pregnancy and lactation is linked to metabolic disturbances and neurodevelopmental problems in offspring, increasing the risk of psychiatric disorders in adulthood. We proposed that maternal N-acetyl cysteine (NAC) supplementation during lactation, a critical period for neurodevelopment, potentially protects offspring from developing cognitive impairment in adulthood. Fifteen young female ICR mice were randomly allocated to different experimental groups: high-fat diet (HFD; 60.3% fat before mating, during pregnancy and lactation), HFD-NAC of 300 mg/kg/day during lactation, CD (high-fat diet before mating, during pregnancy, and regular chow control diet of 8.2% fat during lactation), CD-NAC of 300 mg/kg/day during lactation and control group consuming regular chow diet. The serum inflammatory markers of the offspring were evaluated post-weaning, while metabolic markers, microglial density, and cognitive performance were assessed in adulthood using the novel Object Recognition and Morris Water Maze tests. Our results demonstrate maternal obesity during gestation and lactation increased body weight, hepatic steatosis, and microglial cell density in the dentate gyrus (DG) and cortex. Furthermore, these offspring exhibited reduced spatial learning abilities in adulthood, regardless of sex. However, maternal NAC administration during lactation and maternal diet intervention significantly reduced brain microglial density and improved both male and female offspring metabolic profiles. More importantly, NAC supplementation during lactation, regardless of maternal diet, enhanced male offspring's learning ability in adulthood. Our findings indicate that administering NAC to obese mothers during the critical lactation period may offer protection against metabolic disturbances and cognitive deficits in adult offspring previously exposed to maternal obesity.
孕期和哺乳期的母体肥胖与后代的代谢紊乱和神经发育问题有关，会增加成年后患精神疾病的风险。我们提出，在神经发育的关键时期哺乳期补充母体N-乙酰半胱氨酸（NAC），可能会保护后代在成年后不发生认知障碍。将15只年轻的雌性ICR小鼠随机分配到不同的实验组：高脂饮食组（HFD；交配前、孕期和哺乳期脂肪含量为60.3%）、哺乳期给予300 mg/kg/天NAC的HFD组、CD组（交配前和孕期高脂饮食，哺乳期给予脂肪含量为8.2%的常规饲料对照饮食）、哺乳期给予300 mg/kg/天NAC的CD组以及食用常规饲料饮食的对照组。断奶后评估后代的血清炎症标志物，成年后使用新物体识别和莫里斯水迷宫试验评估代谢标志物、小胶质细胞密度和认知表现。我们的结果表明，孕期和哺乳期的母体肥胖会增加后代体重、肝脂肪变性以及齿状回（DG）和皮质中的小胶质细胞密度。此外，无论性别如何，这些后代在成年后均表现出空间学习能力下降。然而，哺乳期给予母体NAC和母体饮食干预显著降低了脑小胶质细胞密度，并改善了雄性和雌性后代的代谢状况。更重要的是，哺乳期补充NAC，无论母体饮食如何，均可提高雄性后代成年后的学习能力。我们的研究结果表明，在关键的哺乳期给肥胖母亲服用NAC，可能会预防成年后代先前因母体肥胖而出现的代谢紊乱和认知缺陷。
