Researchers exploring the link between newborn infections and later behavior and movement problems have found that inflammation in the brain keeps cells from accessing iron at a critical time in brain development.
Specific cells in the brain need iron to produce the white matter that ensures efficient communication among cells in the central nervous system. White matter refers to white-colored bundles of myelin, a protective coating on the axons that project from the main body of a brain cell.
Scientists from Ohio State University induced a mild E. coli infection in 3-day-old mice. This caused a transient inflammatory response in their brains that was resolved within 72 hours.
This brain inflammation, although fleeting, interfered with the storage and release of iron. This meant that iron avaiaibilty in the brain was temporarily reduced.
When the iron was needed most, it was unavailable, researchers say.
Jonathan Godbout, associate professor of neuroscience at the university and senior author of the study, explains:
“What’s important is that the timing of the inflammation during brain development switches the brain’s gears from development to trying to deal with inflammation. The consequence of that is this abnormal iron storage by neurons that limits access of iron to the rest of the brain.”
The cells that need iron during this critical period of development are called oligodendrocytes, which produce myelin and wrap it around axons. In the current study, neonatal infection caused neurons to increase their storage of iron, which deprived iron from oligodendrocytes.
In other mice, the scientists confirmed that neonatal E. coli infection was associated with motor coordination problems and hyperactivity 2 months later – the equivalent to young adulthood in humans.
The brains of these same mice contained lower levels of myelin and fewer oligodendrocytes, suggesting that brief reductions in brain iron availability during early development have long-lasting effects on brain myelination.
The timing of infection in newborn mice generally coincides with the late stages of the third trimester of pregnancy in humans. The myelination process begins during fetal development and continues after birth.
Jonathan Godbout told Medical News Today:
“About 90% of early onset infections occur within 24 hours of birth. The majority of early onset infections are derived from maternal sources during the birthing process. Incidence of infection drops off dramatically after the first 24 hours, but late onset infections occuring between 4-90 days are still relatively common and are derived from the caregiving environment.”
He went on to say:
“In our study, the strain of E.coli used was “weak” and cleared within 72 hours. Nonetheless, the effects of this transient inflammatory insult on myelination, iron homeostasis in the brain and behavior was profound.”
Though other researchers have observed links between newborn infections and effects on myelin and behavior, scientists had not figured out why. Godbout’s study focuses on understanding how immune system activation can trigger unexpected interactions between the central nervous system and other parts of the body.
“We’re not the first to show early inflammatory events can change the brain and behavior, but we’re the first to propose a detailed mechanism connecting neonatal inflammation to physiological changes in the central nervous system,” says Daniel McKim, a lead author on the paper and a student in Ohio State’s Neuroscience Graduate Studies Program.
The neonatal infection caused several changes in brain physiology. For example, infected mice had increased inflammatory markers, altered neuronal iron storage, and reduced oligodendrocytes and myelin in their brains.
Importantly, the impairments in brain myelination corresponded with behavioral and motor impairments 2 months after infection.
Although it is not known if these movement problems would last a lifetime, McKim noted that “since these impairments lasted into what would be young adulthood in humans, it seems likely to be relatively permanent.”
The reduced myelination linked to movement and behavior issues in this study has also been associated with schizophrenia and autism spectrum disorders in previous work by other scientists, said Godbout, also an investigator in Ohio State’s Institute for Behavioral Medicine Research (IBMR).
“More research in this area could confirm that human behavioral complications can arise from inflammation changing the myelin pattern. Schizophrenia and autism disorders are part of that.”
This current study did not identify potential interventions to prevent these effects of early-life infection. Godbout and colleagues theorize that maternal nutrition – a diet high in antioxidants, for example – might help lower the inflammation in the brain that follows a neonatal infection.
“The prenatal and neonatal period is such an active time of development,” Godbout said. “That’s really the key – these inflammatory challenges during critical points in development seem to have profound effects. We might just want to think more about that clinically.”
Talking to Medical News Today, Godbout added:
“E.coli is a leading cause of neonatal infection. Estimates of neonatal infection vary from 1-8/1000 births. Neonatal infection is particularly common in low birth weight infants and is as high as 160-300/1000 births in this population. Neonatal infection rates are constantly improving, due to increased maternal/infant screenings and effective antibiotic prophylaxis approaches.”