The human milk component myo -inositol promotes neuronal connectivity

Author:

Paquette Andrew F.1ORCID,Carbone Beatrice E.2,Vogel Seth2ORCID,Israel Erica3,Maria Sarah D.4,Patil Nikita P.3,Sah Saroj1ORCID,Chowdhury Dhrubajyoti1,Kondratiuk Ilona1,Labhart Beau4,Morrow Ardythe L.5,Phillips Shay C.4ORCID,Kuang Chenzhong6,Hondmann Dirk6,Pandey Neeraj7ORCID,Biederer Thomas123ORCID

Affiliation:

1. Department of Neurology, Yale School of Medicine, New Haven, CT 06511

2. Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111

3. United States Department of Agriculture Human Nutrition Research Center on Aging, Boston, MA 02111

4. Global Analytical Sciences, Reckitt/Mead Johnson Nutrition, Evansville, IN 47712

5. Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Cincinnati, OH 45229

6. Global Discovery, Mead Johnson Nutrition, Evansville, IN 47712

7. Medical and Scientific Affairs, Reckitt, Slough SL1 3UH, United Kingdom

Abstract

Effects of micronutrients on brain connectivity are incompletely understood. Analyzing human milk samples across global populations, we identified the carbocyclic sugar myo -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. Myo -inositol promoted synapse abundance in human excitatory neurons as well as cultured rat neurons and acted in a dose-dependent manner. Mechanistically, myo -inositol enhanced the ability of neurons to respond to transsynaptic interactions that induce synapses. Effects of myo -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 myo -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 myo -inositol as a breast milk component that promotes the formation of neuronal connections.

Funder

Reckitt Benckiser Pharmaceuticals

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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