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. 2022 Aug 17;27(8):247.
doi: 10.31083/j.fbl2708247.

Sphingomyelin in Human Breast Milk might be Essential for the Hippocampus Maturation

Elisabetta Albi  1 , Cataldo Arcuri  2 , Toshihide Kobayashi  3   4 , Nario Tomishige  3   4 , Michele Dei Cas  5 , Rita Paroni  5 , Paola Signorelli  5 , Laura Cerquiglini  6 , Stefania Troiani  6 , Chiara Gizzi  6 , Maria Rachele Ceccarini  1 , Alessandra Mirarchi  2 , Lina Cossignani  1 , Mercedes Garcia Gil  7   8 , Tommaso Beccari  1 , Samuela Cataldi  1
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Free article

Sphingomyelin in Human Breast Milk might be Essential for the Hippocampus Maturation

Elisabetta Albi et al. Front Biosci (Landmark Ed). .
Free article

Abstract

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.

Keywords: cell differentiation; embryonic hippocampal cells; human milk; neurites; sphingomyelin.

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Conflict of interest statement

The authors declare no conflict of interest. SC is serving as one of the Editorial Board member of this journal. We declare that SC had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to TH.

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