Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin 300070, China.
Int J Mol Sci. 2022 Jun 22;23(13):6948. doi: 10.3390/ijms23136948.
Early life stage folate status may influence neurodevelopment in offspring. The developmental origin of health and disease highlights the importance of the period of the first 1000 days (from conception to 2 years) of life. This study aimed to evaluate the effect of early life stage folic acid deficiency on de novo telomere synthesis, neurobehavioral development, and the cognitive function of offspring rats. The rats were divided into three diet treatment groups: folate-deficient, folate-normal, and folate-supplemented. They were fed the corresponding diet from 5 weeks of age to the end of the lactation period. After weaning, the offspring rats were still fed with the corresponding diet for up to 100 days. Neurobehavioral tests, folic acid and homocysteine (Hcy) levels, relative telomere length in brain tissue, and uracil incorporation in telomere in offspring were measured at different time points. The results showed that folic acid deficiency decreased the level of folic acid, increased the level of Hcy of brain tissue in offspring, increased the wrong incorporation of uracil into telomeres, and hindered de novo telomere synthesis. However, folic acid supplementation increased the level of folic acid, reduced the level of Hcy of brain tissue in offspring, reduced the wrong incorporation of uracil into telomeres, and protected de novo telomere synthesis of offspring, which was beneficial to the development of early sensory-motor function, spatial learning, and memory in adolescence and adulthood. In conclusion, early life stage folic acid deficiency had long-term inhibiting effects on neurodevelopment and cognitive function in offspring.
早期生命阶段叶酸状态可能会影响后代的神经发育。健康与疾病的发育起源强调了生命最初 1000 天（从受孕到 2 岁）这段时期的重要性。本研究旨在评估早期生命阶段叶酸缺乏对新生端粒合成、神经行为发育和后代大鼠认知功能的影响。将大鼠分为三组进行饮食处理：叶酸缺乏组、叶酸正常组和叶酸补充组。从 5 周龄到哺乳期结束，它们分别喂食相应的饮食。断奶后，后代大鼠仍继续喂食相应的饮食，最多 100 天。在不同时间点测量神经行为测试、叶酸和同型半胱氨酸（Hcy）水平、脑组织中相对端粒长度以及后代中端粒的尿嘧啶掺入情况。结果表明，叶酸缺乏降低了叶酸水平，增加了后代脑组织中 Hcy 的水平，增加了端粒中尿嘧啶的错误掺入，阻碍了新生端粒的合成。然而，叶酸补充增加了叶酸的水平，降低了后代脑组织中 Hcy 的水平，减少了端粒中尿嘧啶的错误掺入，保护了后代新生端粒的合成，这有利于青春期和成年期早期感觉运动功能、空间学习和记忆的发展。总之，早期生命阶段叶酸缺乏对后代的神经发育和认知功能有长期的抑制作用。
