Importance of phospholipids for brain development

The investigation of fatty acid composition, not only in total lipids but also in phospholipids contained in human milk. While phospholipids can be considered an important source of energy, they also afford long-chain polyunsaturated fatty acids (LC-PUFAs), which play a pivotal role in growth and brain development in newborn Infants.

Phospholipids are important molecules which form membrane lipid bilayers; they are ubiquitous to every cell in the brain, and carry out a host of different functions. Phospholipids play a key role in supporting the integrity, structure, and function of cells in the brain and the protective myelin sheath. Disruption in brain phospholipids content such as imbalance in phospholipid metabolism, signaling and transport has been documented in some neurological conditions.

One of the most abundant lipids in the brain is sphingomyelin (SM), which is also one of the most abundant phospholipids in human milk, making up 27% of the lipid content in human milk. the high content of SM is considered of importance for infants as it contributes approximate 17% of the total choline to the neonates. The effect of dietary SM has been demonstrated in both preclinical and clinical studies. Clinically, a very low birth weight preterm infants fed with high SM containing formula was shown to be associated with improved behavior rating scores, information processing, and sustained attention at 18 months. Recently, an observational study reported an association of SM as well as phosphatidylcholine (PC) in myelination. The data suggest that dietary intake of these components may be important during the rapid brain development period.

This presentation summarizes the current understanding of the impact of phospholipids in brain development.

16 min watch

Brain development in early life

Infancy and the early years of life are exceptionally dynamic periods of structural and functional development in the human brain. The profound increase in brain size during this period is accompanied by an increase in connectivity, i.e. growth of neural connections in the grey matter (synapse and dendrites), formation of long-range axons, and myelination.1

Myelination is a key neurodevelopmental process in which nerve fibres (axons) are wrapped in lipid-rich sheath that protects the neuron and facilitates fast, efficient and synchronized communication between cells and networks.2,3 Clinical studies demonstrate the link between myelination and cognition, including general cognitive ability, language and reading, working memory, processing speed, and sensory reactivity.2,4,5,6,7

Nutrition and brain development

Early life nutrition is an important and modifiable factor that can influence myelination and, consequently, cognitive outcomes.8 For instance, malnourished infants develop significantly less volume of both grey and white matter,9,10 and that brain connectivity in well-nourished children is much more extensive compared with stunted children of the same age [Figure 1].11

Representation of brain connectivity differences in stunted versus well-nourished children

Figure 1. Representation of brain connectivity differences in stunted versus well-nourished children. Adapted from Kakietek, et al (2017).
 

Apart from being an important source of energy, milk phospholipids are also an important source of long-chain polyunsaturated fatty acids (LC-PUFAs), which play a pivotal role in growth and brain development in newborn Infants.12 Phospholipids are important molecules which form membrane lipid bilayers and play a key role in supporting the integrity, structure, and function of cells in the brain and the protective myelin sheath. One of the most abundant lipids in the brain is sphingomyelin, which is also one of the most abundant phospholipids in human milk, making up 27% of the lipid content in human milk.13,14

Dietary sphingomyelin and cognitive development

In very low birth weight preterm infants, the use of sphingomyelin-fortified formula was demonstrated to be associated with improved behaviour rating scores, information processing, and sustained attention at 18 months.15 These findings are complemented by a more recent exploratory observational study that investigated the link between early life dietary sphingomyelin and later cognitive development and myelination.16 The consumption of infant nutrition products with higher levels of sphingomyelin (28–71 mg/l) was positively correlated with changes in myelination in specific brain regions in the first two years of life. Sphingomyelin levels were also positively correlated with cognitive performance and verbal functioning (e.g., auditory comprehension and memory, speaking ability and language formation) appearing to be more sensitive to early life nutrition than non-verbal functioning. Higher levels of sphingomyelin in the first three months of life were associated with higher levels of brain myelin content in the second year of life, with a later onset but more prolonged rate of myelination.

Summary

The first years of life are a rapid and dynamic period for brain maturation. Most brain processes during this period are primarily focused on connecting the brain, e.g. myelination.  Early life nutrition is an important and modifiable factor that can shape myelination and, consequently, cognitive outcomes. Lipids, particularly phospholipids and sphingomyelin, play an important role in brain, myelin and cognitive development.


Reference:

  1. Tau GZ, Peterson BS. Neuropsychopharmacology. 2010 Jan;35(1):147-68.
  2. Schmithorst VJ, et al. Hum Brain Mapp. 2005 Oct;26(2):139-47.
  3. Deoni SC, et al. J Neurosci. 2011 Jan 12;31(2):784-91.
  4. Nagy Z, et al. J Cogn Neurosci. 2004 Sep;16(7):1227-33.
  5. Büchel C, et al. Cereb Cortex. 2004 Sep;14(9):945-51.
  6. Turken A, et al. Neuroimage. 2008 Aug 15;42(2):1032-44.
  7. Weinstein M, et al. Neuropsychologia. 2014 Sep;62:209-19.
  8. Deoni S, et al. Neuroimage. 2018 Sep;178:649-659.
  9. Nelson CA. Brain Imaging as a.Measure of Future Cognitive Outcomes. Presentation at Early Child Development Measurement Framework, World Health Organization, January 17–19, 2017.
  10. Bendini M. Adversity gets in the brain. Available at: https://blogs.worldbank.org/developmenttalk/adversity-gets-brain. Accessed June 2021.
  11. Kakietek, Jakub, Julia Dayton Eberwein, Dylan Walters, and Meera Shekar. 2017. Unleashing Gains in Economic Productivity with Investments in Nutrition. Washington, DC: World Bank Group.
  12. Ingvordsen Lindahl IE, et al. Nutrients. 2019 Jan 22;11(2):222.
  13. Zheng L, et al. Adv Nutr. 2019 Nov 1;10(6):1163-1176.
  14. Thakkar SK, et al. Am J Hum Biol. 2013 Nov-Dec;25(6):770-9.
  15. Tanaka K, et al. Brain Dev. 2013 Jan;35(1):45-52.
  16. Schneider N, et al. eNeuro. 2019 Aug 6;6(4):ENEURO.0421-18.2019.