Société des Produits Nestlé SA, Nestlé Research, 1000 Lausanne, Switzerland.
Société des Produits Nestlé SA, Nestlé Research, 1000 Lausanne, Switzerland
eNeuro. 2019 Aug 6;6(4). doi: 10.1523/ENEURO.0421-18.2019. Print 2019 Jul/Aug.
Sphingomyelin (SM) supports brain myelination, a process closely associated with cognitive maturation. The presence of SM in breast milk suggests a role in infant nutrition; however, little is known about SM contribution to healthy cognitive development. We investigated the link between early life dietary SM, later cognitive development and myelination using an exploratory observational study of neurotypical children. SM levels were quantified in infant nutrition products fed in the first three months of life and associated with myelin content (brain MRI) as well as cognitive development (Mullen scales of early learning; MSEL). Higher levels of SM were significantly associated with higher rates of change in verbal development in the first two years of life ( = 0.65, < 0.001), as well as, higher levels of myelin content at 12-24 months, delayed onset and/or more prolonged rates of myelination in different brain areas. Second, we explored mechanisms of action using in vitro models (Sprague Dawley rat pups). In vitro data showed SM treatment resulted in increased proliferation [ = 0.0133 and = 0.0434 at 4 and 10 d (DIV)], maturation ( = 0.467 at 4 d DIV) and differentiation ( = 0.0123 and = 0.0369 at 4 and 10 DIV) of oligodendrocyte precursor cells (OPCs), as well as increased axon myelination ( = 0.0005 at 32 DIV). These findings indicate an impact of dietary SM on cognitive development in healthy children, potentially modulated by oligodendrocytes and increased axon myelination. Future research should include randomized controlled trials to substantiate efficacy of SM for cognitive benefits together with preclinical studies examining SM bioavailability and brain uptake.
鞘磷脂 (SM) 支持脑髓鞘形成,这一过程与认知成熟密切相关。母乳中存在 SM 表明其在婴儿营养中具有一定作用;然而,目前对于 SM 对健康认知发育的贡献知之甚少。我们通过对神经正常的儿童进行探索性观察研究,调查了生命早期饮食 SM 与之后的认知发育和髓鞘形成之间的关系。我们在婴儿生命的头三个月内所摄入的婴儿营养产品中定量了 SM 水平,并将其与髓鞘含量(脑 MRI)以及认知发育(Mullen 早期学习量表;MSEL)相关联。SM 水平较高与生命前两年言语发育的变化率更高呈显著正相关( = 0.65, < 0.001),并且在 12-24 个月时与髓鞘含量较高、不同脑区髓鞘形成的起始延迟和/或更长时间相关。其次,我们使用体外模型(Sprague Dawley 幼鼠)探索了作用机制。体外数据表明,SM 处理可导致增殖增加[4 d 和 10 d 时(DIV)分别为 = 0.0133 和 = 0.0434]、成熟(4 d DIV 时为 = 0.467)和分化(4 d 和 10 DIV 时分别为 = 0.0123 和 = 0.0369),少突胶质前体细胞(OPCs),以及轴突髓鞘形成增加(32 DIV 时为 = 0.0005)。这些发现表明,饮食 SM 对健康儿童的认知发育具有影响,其作用可能通过少突胶质细胞和增加的轴突髓鞘形成来调节。未来的研究应包括随机对照试验,以证实 SM 对认知益处的功效,同时还应进行研究 SM 生物利用度和大脑摄取的临床前研究。