A blend containing docosahexaenoic acid, arachidonic acid, vitamin B12, vitamin B9, iron and sphingomyelin promotes myelination in an in vitro model

ABSTRACT

During the development of the central nervous system, oligodendrocytes (OLs) are responsible for myelination, the formation of the myelin sheath around axons. This process enhances neuronal connectivity and supports the maturation of emerging cognitive functions. In humans, recent evidence suggests that early life nutrition may affect myelination. In the present study, we investigated the impact of a blend containing docosahexaenoic acid, arachidonic acid, vitamin B12, vitamin B9, iron and sphingomyelin, or each of these nutrients individually, on oligodendrocyte precursor cells (OPCs) proliferation and maturation into OLs as well as their myelinating properties. By using an in vitro model, developed to study each step of myelination, we found that the nutrient blend increased the number of OPCs and promoted their differentiation and maturation into OLs, as measured by quantifying A2B5 positive cells, myelin-associated glycoprotein (MAG) positive cells and area, myelin binding protein (MBP) positive cells and area, respectively. Moreover, measuring myelination by quantifying the overlapping signal between neurofilament and either MAG or MBP revealed a positive effect of the blend on OLs myelinating properties. In contrast, treatment with each individual nutrient resulted in differential effects on the various readouts. This work suggests that dietary intake of these nutrients during early life, might be beneficial for myelination.

KEYWORDS:

• Oligodendrocyte
• myelination
• sphingomyelin
• DHA
• ARA
• vitamin B9
• vitamin B12
• iron

Acknowledgements

We thank R&D collaborators at Nestlé Research. We thank Dr. Maud Combes and Dr. Noëlle Callizot (Neuro-Sys SA) for their advices on the study design. We also thank Dr. Barry O’Neill and Sarah Costello (Nestec Ltd., Nestlé Research) for proofreading the manuscript.

Disclosure statement

JH, SS, AR, PS and NS are employees of Nestec Ltd.

Notes on contributors

Jonas Hauser obtained his Ph.D. at the Swiss Institute of Technology - Zurich in 2007. He then worked as a postdoctoral researcher at the Swiss Institute of Technology - Zurich and University College London prior to joining the Nestlé Institute for Health Sciences as a specialist in cognition. His topics include nutrition to support neurodevelopment, nutrition to help mitigate neurological disease symptoms and the cellular and molecular mechanisms mediating these nutritional effects.

Sébastien Sultan obtained a Ph.D. in Neuroscience at the University of Lyon, Université Claude Bernard Lyon 1, France in 2010. He then worked in the Department of Fundamental Neurosciences, University of Lausanne, Switzerland as a postdoctoral researcher prior to joining the Nestlé Institute of Health Sciences and then Nestlé Research in Lausanne, Switzerland as a scientist in Neurobiology.

Andreas Rytz received his M.Sc. in mathematics from the Swiss Federal Institute of Technology in 1992, and he joined Nestlé Research Center in Lausanne in 1993. He is a senior data analyst focussing on design of experiments and statistical modeling applied to life sciences (in vitro, in vivo, clinical trials), sensometrics, chemometrics and bioinformatics.

Dr Pascal Steiner received his B.Sc. from the University of Lausanne, a Ph.D. in Neuroscience from the Swiss Federal Institute of Technology in 2004, and completed a postdoctoral fellowship at Harvard Medical School in 2008. He then served as Director of Operations at Tilocor International, a biotech consortium, where he supervised the transfer process of drug candidate products from research towards clinical development. From 2010 to 2015, Dr Steiner worked in the Neuroscience Department at Genentech in South San Francisco, leading an interdisciplinary team to discover and develop new drug targets in neurological diseases, including amyotrophic lateral sclerosis, Alzheimer’s disease, and pain. In 2015, Dr Steiner joined the Nestlé Institute of Health Science in Lausanne, Switzerland and was then appointed Head of the Department of Brain Health. Its mission is to identify and develop innovative nutritional solutions to support brain health throughout life, including programs focusing on infant neurodevelopment and cognition, working with Wyeth Nutrition.

Nora Schneider obtained her Diplom in Psychology and her Ph.D. in the area of Alzheimer’s disease and neuropsychiatry of ageing at the Free University Berlin and the Charité - University Hospital Berlin, Germany. She worked in the Department of Child and Adolescent Psychiatry of the Charité - University Hospital Berlin, Germany, as both researcher and psychotherapist in training for cognitive-behavioral therapy in children and adolescents prior to joining Nestlé Research in 2010 where she currently leads the Neurocognition group. Her topics include the scientific evaluation of nutritional solutions for brain and cognitive development, cognitive decline and brain health as well as the design and management of clinical studies.