IMR Press / FBL / Volume 27 / Issue 8 / DOI: 10.31083/j.fbl2708247
Open Access Original Research
Sphingomyelin in Human Breast Milk might be Essential for the Hippocampus Maturation
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1 Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy
2 Department of Experimental Medicine, University of Perugia, 06123 Perugia, Italy
3 UMR 7021 CNRS, Université de Strasbourg, 67401 Illkirch, France
4 Cellular Informatics Laboratory, RIKEN, Wako, 351-0198, Saitama, Japan
5 Department of Health Sciences, Università degli Studi di Milano, 20142 Milan, Italy
6 Struttura Complessa di Neonatologia e Terapia Intensiva Neonatale-Azienda Ospedaliera Santa Maria della Misericordia, 06126 Perugia, Italy
7 Department of Biology, University of Pisa, 56127 Pisa, Italy
8 Interdepartmental Research Center “Nutraceuticals and Food for Health'', University of Pisa, 56127 Pisa, Italy
*Correspondence: (Samuela Cataldi)
Academic Editor: Thomas Heinbockel
Front. Biosci. (Landmark Ed) 2022, 27(8), 247;
Submitted: 24 April 2022 | Revised: 21 July 2022 | Accepted: 8 August 2022 | Published: 17 August 2022
(This article belongs to the Special Issue Advances in Sphingolipids)
Copyright: © 2022 The Author(s). Published by IMR Press.

This is an open access article under the CC BY 4.0 license.


Background: It has been established that sphingomyelin present human breast milk is useful for the brain maturation and cognitive development. At 10 days of breastfeeding the sphingomyelin content is double that present in cow’s milk and its content is independent of the maternal diet. The aim of the study was to analyze the content of sphingomyelin in breast milk at 3 months of breastfeeding and to consider the effect of this molecule on synaptic function and nerve conduction through the probable expansion of myelinated axons. Methods: Therefore, to begin to define and assess this, we performed sphingolipidomic analysis in human breast milk. Then, we cultured embryonic hippocampal cells (HN9.10) in the presence of sphingomyelin at a concentration from 0.6% to 31% of human milk, estimated by considering its bioavailability and its passage into the interstitial fluid. To highlight the effect of sphingomyelin in the cells, cell viability and morphology were evaluated. Analyses of neutral sphingomyelinase gene and protein expression was performed. The entry of sphingomyelin into the cell was studied in immunofluorescence; the expression of heavy neurofilament (NF200) was tested with immunocytochemical technique. Results: We demonstrated that sphingomyelin is able to enter cell nucleus and overexpress the sphingomyelin phosphodiesterase 4 (SMPD4) gene encoding for neutral sphingomyelinase (nSMase), an enzyme useful for its own metabolism. Later, cells displayed changes of the soma and the appearance of neurites supported by NF200 overexpression. Conclusions: We speculated that the sphingomyelin present in human breast milk is useful in part to regulate nuclear activity and in part to form myelin sheet to facilitate nerve cell maturation. As brain development occurs at 0–3 years, these data open a new avenue of potential intervention to integrate the infant formulas with SM to obtain a product similar to the maternal milk.

human milk
embryonic hippocampal cells
cell differentiation
Fig. 1.
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