Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
Nutr Neurosci. 2012 Mar;15(2):55-61. doi: 10.1179/1476830511Y.0000000025. Epub 2012 Jan 13.
Increasing neurogenesis may restore cognitive functions that are impaired in ischemia stroke. Folic acid has been reported to play an important role in neuronal development and reduce the risk of ischemic stroke in primary prevention. Folic acid supplementation stimulates Notch signaling and cell proliferation in neural progenitor cells cultured from neonatal brain. The present study determined whether folic acid supplementation stimulates Notch signaling and neurogenesis and improves cognitive function after ischemic stroke in adult brain. Rats were randomly assigned to four groups: sham operation plus vehicle (Sham), middle cerebral artery occlusion plus vehicle (MCAO), MCAO plus low-dose folic acid (4 mg/(kg day)), and MCAO plus high folic acid (12 mg/(kg day)). The vehicle and folic acid were administered by oral gavage for 28 days prior to sham or MCAO operation and up to 14 days after surgery. Newborn hippocampal neurons were detected at 3, 7, and 14 days post-MCAO. Cognitive function (learning and memory in Y-maze tests) and the protein expression levels of components of the Notch signaling system (Notch1, Hes1, and Hes5) were measured at 7 days post-MCAO. The results showed that MCAO impaired Y-maze performance and stimulated Notch signaling and hippocampal neurogenesis in brain. Folic acid prevented the impairment of Y-maze performance. The nutrient also increased further the expression of Notch1, Hes1, and Hes5 and the number of the newborn hippocampal neurons. Folic acid enhances the stimulation by ischemia of Notch signaling and hippocampal neurogenesis in adult brain and lessens the impairment of cognitive function that occurs after experimental stroke.
增加神经发生可能恢复缺血性中风受损的认知功能。已报道叶酸在神经元发育中发挥重要作用，并可降低一级预防中缺血性中风的风险。叶酸补充剂可刺激神经祖细胞中的 Notch 信号和细胞增殖，这些细胞来自新生大脑。本研究旨在确定叶酸补充是否可刺激 Notch 信号和神经发生，并改善成年大脑缺血性中风后的认知功能。大鼠随机分为四组：假手术+载体（Sham）、大脑中动脉闭塞+载体（MCAO）、MCAO+低剂量叶酸（4mg/（kg·天））和 MCAO+高叶酸（12mg/（kg·天））。载体和叶酸通过口服灌胃给药，在 Sham 或 MCAO 手术前 28 天给药，并持续至手术后 14 天。在 MCAO 后 3、7 和 14 天检测新生海马神经元。在 MCAO 后 7 天测量认知功能（Y 迷宫测试中的学习和记忆）和 Notch 信号系统成分（Notch1、Hes1 和 Hes5）的蛋白表达水平。结果表明，MCAO 损害了 Y 迷宫表现，刺激了 Notch 信号和海马神经发生。叶酸可防止 Y 迷宫表现受损。这种营养素还进一步增加了 Notch1、Hes1 和 Hes5 的表达以及新生海马神经元的数量。叶酸增强了缺血对成年大脑 Notch 信号和海马神经发生的刺激，并减轻了实验性中风后认知功能的损害。
