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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.

It has long been proven that neurogenesis continues in the adult brains of mammals in the dentatus gyrus of the hippocampus due to the presence of neural stem cells. Although a large number of studies have been carried out to highlight the localization of vitamin D receptor in hippocampus, the expression of vitamin D receptor in neurogenic dentatus gyrus of hippocampus in Parkinson’s disease (PD) and the molecular mechanisms triggered by vitamin D underlying the production of differentiated neurons from embryonic cells remain unknown. Thus, we performed a preclinical in vivo study by inducing PD in mice with MPTP and showed a reduction of glial fibrillary acidic protein (GFAP) and vitamin D receptor in the dentatus gyrus of hippocampus. Then, we performed an in vitro study by inducing embryonic hippocampal cell differentiation with vitamin D. Interestingly, vitamin D stimulates the expression of its receptor. Vitamin D receptor is a transcription factor that probably is responsible for the upregulation of microtubule associated protein 2 and neurofilament heavy polypeptide genes. The latter increases heavy neurofilament protein expression, essential for neurofilament growth. Notably N-cadherin, implicated in activity for dendritic outgrowth, is upregulated by vitamin D.

It has long been proven that neurogenesis continues in the adult brains of mammals in the dentatus gyrus of the hippocampus due to the presence of neural stem cells. Although a large number of studies have been carried out to highlight the localization of vitamin D receptor in hippocampus, the expression of vitamin D receptor in neurogenic dentatus gyrus of hippocampus in Parkinson's disease (PD) and the molecular mechanisms triggered by vitamin D underlying the production of differentiated neurons from embryonic cells remain unknown. Thus, we performed a preclinical in vivo study by inducing PD in mice with MPTP and showed a reduction of glial fibrillary acidic protein (GFAP) and vitamin D receptor in the dentatus gyrus of hippocampus. Then, we performed an in vitro study by inducing embryonic hippocampal cell differentiation with vitamin D. Interestingly, vitamin D stimulates the expression of its receptor. Vitamin D receptor is a transcription factor that probably is responsible for the upregulation of microtubule associated protein 2 and neurofilament heavy polypeptide genes. The latter increases heavy neurofilament protein expression, essential for neurofilament growth. Notably N-cadherin, implicated in activity for dendritic outgrowth, is upregulated by vitamin D. [ABSTRACT FROM AUTHOR]

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., Competing Interests: 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., (© 2022 The Author(s). Published by IMR Press.)

The understanding of the mechanism of apoptosis is important to improve the use of stem cells for the treatment of neurodegenerative disorders. Sphingolipids are bioactive molecules involved in the regulation of cell fate. In HN9.10e embryonic hippocampal cells, serum deprivation induces apoptosis preceded by sphingomyelinase activation and raise of ceramide levels. Increasing evidence indicates that individual ceramide species regulated by specific pathways in distinct subcellular compartments might carry out distinct cellular functions, but the ceramides species involved in embryonic hippocampal cell death induced by growth factor deprivation are unknown. In the present paper, by using the UFLC-MS/MS methodology, we have investigated the effect of serum deprivation on the lipid profile in HN9.10e cells. At 48h of serum deprivation, we detected a decrease in cholesterol and increase in sphingosine-1-phoshate 18:1, phosphatidylcholine 18:1 18:0, sphingomyelin 18:1 16:0 and in ceramides 18:1 16:0; we also found an increase in saturated/unsaturated fatty acid ratio in sphingomyelin. We hypothesize that the rearrangement of sphingo- and glycerolipids with increase of saturated fatty acids in serum-deprivated, neural cells might represent a cellular response aimed at holding cholesterol inside the cells., (Copyright © 2015. Published by Elsevier Ireland Ltd.)