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 that they need to perform a critical role 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.
The scientists 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, researchers say.
"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," said Jonathan Godbout, associate professor of neuroscience at The Ohio State University and senior author of the study. "The consequence of that is this abnormal iron storage by neurons that limits access of iron to the rest of the brain."
The research is published in the Oct. 9, 2013, issue of the Journal of Neuroscience.
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 two 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.
Though other researchers have observed links between newborn infections and effects on myelin and behavior, scientists had not figured out why those associations exist. Godbout's group 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," said 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 two months after infection.
Though it's unknown 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," he said.
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."
This work is the result of close collaboration between Godbout; Ning Quan and Michael Bailey of Ohio State's Division of Oral Biology and the IBMR; Dana McTigue of Ohio State's Department of Neuroscience and Center for Brain and Spinal Cord Repair; and Staci Bilbo of Duke University. Additional co-authors from Ohio State are Jacqueline Lieblein-Boff (now with Abbott Nutrition), Daniel McKim, Daniel Shea, Ping Wei, Zhen Deng and Caroline Sawicki.
The research was supported by Abbott Nutrition and the National Institutes of Health.
Jonathan Godbout, (614) 293-3456; Jonathan.Godbout@osumc.edu
Written by Emily Caldwell, (614) 292-8310; Caldwell.email@example.com
Jonathan Godbout | EurekAlert!
The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung
A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences