Department of Neurology, Yale School of Medicine, New Haven, CT 06511.
Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111.
Proc Natl Acad Sci U S A. 2023 Jul 25;120(30):e2221413120. doi: 10.1073/pnas.2221413120. Epub 2023 Jul 11.
Effects of micronutrients on brain connectivity are incompletely understood. Analyzing human milk samples across global populations, we identified the carbocyclic sugar -inositol as a component that promotes brain development. We determined that it is most abundant in human milk during early lactation when neuronal connections rapidly form in the infant brain. -inositol promoted synapse abundance in human excitatory neurons as well as cultured rat neurons and acted in a dose-dependent manner. Mechanistically, -inositol enhanced the ability of neurons to respond to transsynaptic interactions that induce synapses. Effects of -inositol in the developing brain were tested in mice, and its dietary supplementation enlarged excitatory postsynaptic sites in the maturing cortex. Utilizing an organotypic slice culture system, we additionally determined that -inositol is bioactive in mature brain tissue, and treatment of organotypic slices with this carbocyclic sugar increased the number and size of postsynaptic specializations and excitatory synapse density. This study advances our understanding of the impact of human milk on the infant brain and identifies -inositol as a breast milk component that promotes the formation of neuronal connections.
微营养素对大脑连接的影响尚不完全清楚。通过分析全球人群的母乳样本，我们发现碳环糖肌醇是促进大脑发育的成分之一。我们确定，在婴儿大脑中神经元连接迅速形成的哺乳期早期，母乳中肌醇的含量最丰富。肌醇可促进人兴奋性神经元和培养的大鼠神经元中突触的丰富，且呈剂量依赖性。在机制上，肌醇增强了神经元响应诱导突触形成的突触间相互作用的能力。在发育中的大脑中测试了肌醇的作用，其饮食补充可增加成熟大脑皮层中兴奋性突触后位点的大小。利用器官型切片培养系统，我们还确定肌醇在成熟脑组织中具有生物活性，用这种碳环糖处理器官型切片可增加突触后特化和兴奋性突触密度的数量和大小。这项研究增进了我们对母乳对婴儿大脑影响的理解，并确定肌醇是促进神经元连接形成的母乳成分之一。
