Scientists investigating the link between newborn infections and behavior and movement problems later in life have found that inflammation in the brain keeps cells from accessing iron that they need to perform a critical role in brain development.
Jonathan Godbout, from Ohio State University and senior author of the study, explained that 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.
To explore further, Godbout and his team 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, though fleeting, interfered with storage and release of iron, temporarily resulting in reduced iron availability in the brain. When the iron was needed most, it was unavailable, Godbout said.
"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," he explained. "The consequence of that is this abnormal iron storage by neurons that limits access of iron to the rest of the brain."
This caused several changes in brain physiology. Godbout said the infected mice had increased inflammatory markers, altered neuronal iron storage, and reduced myelin in their brains. Importantly, the impairments in brain myelination corresponded with behavioral and motor impairments two months after infection.
Though it's unknown if these movement problems would last a lifetime, the researchers note 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 previously associated with schizophrenia and autism spectrum disorders in work by other scientists.
The timing of the infection in the 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.
Though other researchers have observed links between newborn infections and effects on myelin and behavior, scientists had not figured out why those associations exist. "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," said co-researcher Daniel McKim.
"The prenatal and neonatal period is such an active time of development," Godbout concluded. "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."
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Source: Ohio State University