Written by: Alla Katsnelson, Ph.D | Issue # 116 | 2023
- Samples analyzed in a recent study came from a unique repository collected from mothers in Mexico City, Shanghai, and Cincinnati, OH, each time they fed their babies during their first year.
- Amounts of myo-inositol are high in human milk for the first few months after birth, and then decrease, suggesting the molecule is important for infants during that early time.
- myo-inositol promoted the formation of synapses—connections between neurons—in human and rodent cells grown in a dish and in living mice.
It’s no secret that nutrition is a major contributor to health, but scientists know very little about how specific micronutrients affect the brain. Now, new research suggests that a specific carbohydrate in breast milk called myo-inositol enables neurons in the developing brain form connections, called synapses, through which they pass information (1).
“I did not expect that bioactive compounds can so profoundly impact brain development, says Thomas Biederer, a neuroscientist at Yale University School of Medicine and the USDA Human Nutrition Center, who led the work. “I think these effects of micronutrients on the brain are really underappreciated.”
What made the study possible was a repository of milk samples assembled and held by Mead Johnson Nutrition/Reckitt, a company that produces pediatric nutrition products. The repository consists of lactation samples from mothers in Mexico City, Shanghai, and Cincinnati, OH, who collected them each time they fed their babies from birth to 1 year of age.
The company funded the study with the aim of identifying important elements in breast milk that are missing from formula. The researchers analyzed a range of lipids, carbohydrates, and secreted proteins in the samples, but for Biederer, an interesting fact popped out about the level of myo-inositol. “It is high early on, in the first few months after birth, and then it starts to gradually go down,” he says. “That piqued my interest because this is the period when most synapses in the human brain are forming, particularly in brain regions responsible for cognition, in the cerebral cortex.”
During development, neurons initially form an overabundance of synapses (2). This synapse formation occurs over different time periods across different regions. In humans, sensory regions of the cerebral cortex, which process vision, hearing and touch, go through this burst during infancy. In other areas such as the frontal cortex, which is involved in more complex dimensions of cognition, this process lasts through adolescence.
To test whether myo-inositol directly affects how neurons develop, the researchers first applied it to human or rat cells grown in a dish. Treating human cells with myo-inositol did not alter the neurons’ length or the degree of complexity in their branching, but it increased the number of synapses in the cells by 29%. The researchers observed the same effect in rat neurons, also noting that the increase in synapses was greater the more myo-inositol they added.
Biederer and his colleagues fed myo-inositol to mouse pups from birth to 35 days of age, then examined synapses in their visual cortex. They found that the size of synapses increased by about 50%, which likely reflects an increase the in the strength of synapses. Finally, they looked at slices of brain tissue that were taken from young mice and grown in a dish until they reached maturity. They determined that the number of synapses increased after they applied myo-inositol.
“The conclusion is really robust across all models that myo-inositol promotes how nerve cells can form connections between each other,” Biederer says. “The effects were really, really apparent—when we treated the cultured neurons with myo-inositol they looked healthier than anything we had seen before.”
Biederer adds that although the current study focused on myo-inositol, breast milk likely has many other functionally important components. “It’s just the first one we had the opportunity to investigate in detail,” he says.
The idea that micronutrients can have significant effects on brain function is severely understudied, Biederer notes. There were hints in previous research linking the substance to brain function in adults (3, 4), but the study is the first to flag its potential involvement in the infant brain. He cautions that more research is needed before there’s enough evidence to suggest that people should consume myo-inositol to boost brain function.
Biederer’s team is now looking at a slightly later stage of brain development, during which the overproduced connections between neurons get trimmed down so that only the most functional ones remain. “Our interest now is identifying what compounds are supporting the refinement of connectivity,” he says.
References
- Paquette AF, Carbone BE, Vogel S, Israel E, Maria SD, Patil NP, Sah S, Chowdhury D, Kondratiuk I, Labhart B, Morrow AL, Phillips SC, Kuang C, Hondmann D, Pandey N, Biederer T. The human milk component myo-inositol promotes neuronal connectivity. Proc Natl Acad Sci U S A. 2023:25;120(30):e2221413120.
- Rakic P, Bourgeois JP, Eckenhoff MF, Zecevic N, Goldman-Rakic PS. Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science. 1986:232(4747):232-235.
- Vawter MP, Hamzeh AR, Muradyan E, Civelli O, Abbott GW, Alachkar A. Association of myoinositol transporters with schizophrenia and bipolar disorder: Evidence from human and animal studies. Mol Neuropsychiatry. 2019:5(4):200-211.
- Levine J, Barak Y, Gonzalves M, Szor H, Elizur A, Kofman O, Belmaker RH. Double-blind, controlled trial of inositol treatment of depression. Am J Psychiatry. 1995:152(5):792-794.