Changes taking place in a woman's environment while her baby is suckling, such as those that may affect her levels of circulating hormones or cell-signaling molecules, can influence her child's brain development and ultimately his or her physical and behavioral traits, according to new research by Weill Cornell Medical College scientists.
This "lactocrine" pathway, described in the Dec. 1 online edition of Nature Neuroscience, is a new example of "maternal effect," a process through which a child's traits are determined not by his or her own environment and genes, but rather by the environment of the nursing mother, such as her stress level. The process is distinct from those that may affect nursing babies on other measures, such as infection rates and mental health. Senior investigator Dr. Miklos Toth, a professor of pharmacology at Weill Cornell, called the connection a "non-genetic link between mother and offspring" that "prepares the offspring to better cope with their environment."
In humans, for example, a mother may encounter a dramatic change in her environment—emotional stress from war or physical stresses such as famine—that stimulates production of inflammatory proteins, which in turn alter the child's physical or behavioral traits.
The maternal effect has been well documented at the level of populations, particularly in the animal kingdom. The new research from Dr. Toth's lab is important because it breaks down, step by step and for the first time, one way in which the maternal effect is transmitted from mother to child.
The study, which was led by Dr. Bing Fang Liu, an instructor in pharmacology at Weill Cornell, investigated the way in which tumor necrosis factor (TNF), a signaling molecule, may produce a maternal effect between female mice and their offspring. TNF, which is produced in response to injuries and other harmful stimuli, helps combat pathogens in the immune system.
The investigators found that when they genetically inactivated TNF in the mothers, cell-signaling proteins called chemokines were reduced in the mother's breast milk, and their offspring had increased growth in the hippocampus region of the brain, which led to better memory among the offspring. These changes were permanent, persisting into adulthood.
In addition, when the investigators gave the missing chemokines directly to the offspring of TNF-deficient mothers, they found that returning TNF levels to normal produced typical brain development as well as typical memory function in offspring.
To see if prescribed medications might cause a similar effect, the investigators also studied anti-TNF drugs, which suppress the inflammatory response and are commonly used in humans for a wide variety of conditions, from asthma and psoriasis to inflammatory bowel disease and rheumatoid arthritis. When lactating mothers were given a widely prescribed anti-TNF drug, infliximab, the drug led to the same increased growth of the hippocampus and better memory among mice pups as when the mothers were genetically TNF deficient.
Although the study suggested that withholding maternal TNF during newborn development might lead to better memory, Dr. Toth said that the finding was more important to prove the concept of the lactocrine pathway than to demonstrate a means of enhancing memory, which could bring accompanying energy costs that outweigh any benefit. "This is just one of many possible links," Dr. Toth said.
More broadly, the study shows that a mother sends signals to her baby through his or her gut, and that these signals, by changing the immune status of the child, communicate with the brain.
"This is one way in which the mother reaches the offspring's brain development," Dr. Toth said. The evolutionary goal, he added, is for the newborn baby's development to match the environment into which it is born as closely as possible, "and the mother is helping the pup to achieve that."