File:Myo-Inositol Is a Dynamic Component of Human Milk That Peaks Early in Lactation.jpg

English: "Myo-inositol peaks in human milk during early infant brain development and this carbocyclic sugar promotes the abundance and size of excitatory postsynaptic sites in human glutamatergic neurons. (A) Free myo-inositol content in human milk is highest in the first wk of lactation. Samples were longitudinally collected from ten mothers per site in Shanghai, Mexico City, and Cincinnati over 52 wk. Circles, myo-inositol concentration per mother. Lines, mean concentration per geography. (B) Temporal profiles of processes underlying cortical developmental. (C, Top), representative confocal images of human glutamatergic–enriched cortical neurons 24 d after plating, cultured under control conditions (C, Left) or with myo-inositol at 2 mM (C, Right). Immunostainings were performed for presynaptic Bassoon (red), excitatory postsynaptic Homer (green), and dendritic MAP2 (blue). (C, Bottom) enlarged dendritic segments. (D and E) Quantification of images as in C determined that myo-inositol increases in human glutamatergic neurons the abundance of postsynaptic Homer measured as immunostaining intensity per dendritic area (D) and the size of Homer-positive specializations (E). Violin plots show data distribution. Solid lines mark the median and dotted lines the quartiles. Asterisks show statistical differences of mean values, which are not plotted. (Student’s t test, two-tailed unpaired; dendritic segments from N = 86 control/71 myo-inositol-treated neurons) ***P < 0.001. (F and G) Myo-inositol treatment did not significantly increase presynaptic Bassoon abundance (F) and size of Bassoon-positive sites (G). Violin plots show data as in D and E. n.s., not significant."

"Analysis of the GEHM samples determined that free myo-inositol content was consistently high postpartum, with a global mean of 180 ± 41 µg/mL at 2 wk (Fig. 1A and SI Appendix, Table S2). Free myo-inositol intake by infants at 2 wk was estimated as 105 ± 24 mg/day (mean ± SD) (SI Appendix, Table S2). Myo-inositol in human milk subsequently decreased, which was most pronounced after early lactation (Fig. 1A). The myo-inositol profile across the study geographies was indistinguishable, with no difference by country (P = 0.35) (SI Appendix, Table S3). Like free inositol, total inositol concentration decreased over lactation (P < 0.01) with no significant interaction effect of maternal country (P = 0.36) (SI Appendix, Table S4).

Myo-Inositol Promotes in Human Neurons the Abundance of Specializations Positive for the Excitatory Postsynaptic Marker Homer.

The profile of inositol in human milk tracked the peak of synaptogenesis in the infant cortex, a crucial process of postnatal development (1, 2) (Fig. 1B; see also SI Appendix, Supplemental Results). Thus, we aimed to test whether myo-inositol is a human milk compound impacting neuronal connectivity. We analyzed this in human glutamatergic–enriched cortical neurons derived from induced pluripotent stem cells. Immunostaining for the presynaptic active zone marker Bassoon and the excitatory postsynaptic scaffold protein Homer showed that synaptic specializations were formed by 21 d after plating (Fig. 1C)."