The role of oxygen in wiring the brain

Environmental factors like oxygen affect neurons in the brain. Scientists at St. Jude are studying the role oxygen plays in the maturation and migration of neurons. They have identified a new mechanism that helps control these processes.

Rising oxygen levels in the developing cerebellum dial down a biological mechanism called the Hif1α pathway. At low oxygen levels, this pathway inhibits neurons from maturing and migrating. But turning it down even more kick starts their development.

The Hif1α pathway inhibits critical differentiation and polarization processes. Neurons use these processes to migrate to the positions they occupy in mature neuronal circuits.  

The findings are relevant for premature babies that have hypoxic insults, temporary or chronic lack of oxygen in the brain. Such defects could lead to enhanced Hif1α pathway activation.

This study shows such activation blocks neurons’ ability to differentiate and polarize properly. This can cause neurons to fail to migrate and thus be wired incorrectly in developing circuits.

“This finding of the link between oxygen levels and maturation is an important conceptual shift in the field,” said senior author David Solecki, PhD, of Developmental Neurobiology. “It also provides a foundation for better understanding hypoxia and the effect of reduced oxygen to the brain in infants.”

Neuron published a report on this work.