Mild hypoxia in premature infants linked to lifelong memory problems

While in intensive care after premature birth, babies may experience low oxygen—or hypoxia—in their tissues and cells. Hypoxia is associated with poor brain health outcomes and lifelong memory problems, but the mechanisms are unclear. Researchers led by Art Riddle and Stephen Back of Oregon Health & Science University discovered a contributing mechanism by creating a mouse model for mild hypoxia after premature birth. Riddle emphasizes that, “The field has historically focused on how hypoxia damages white matter in the brain and kills neurons. This is the first study to explore how mild hypoxia can alter brain development without direct brain injury in this neonatal period.”

As presented in them jenurosky paper, mild hypoxia soon after birth hinders learning and memory in adulthood, and researchers discovered, at least in part, the mechanism for this effect: altered neuron-to-neuron communication in the hippocampus. Investigating the molecular mechanisms, the researchers found that hypoxia after premature birth affects protein channels involved in neuron-to-neuron communication and memory that develop in the hippocampus during adolescence. They also identified a second protein that was involved in the effects of hypoxia on channel functioning. When the researchers targeted this second protein in adult mice, they restored the channel’s function. “When we looked at surrounding brain regions we also found that this protein was changed by mild hypoxia, which suggests that other brain regions may also be sensitive to hypoxia,” says Riddle. The researchers plan to assess how hypoxia affects these areas in future work.

According to the authors, this work sheds light on how hypoxia in premature infants affects neuron communication in memory-related brain regions and hinders learning and memory in adulthood. Speaking on clinical implications, Riddle says, “We studied here the subtle deficits caused by mild hypoxia that are commonly seen in clinical settings with premature babies.” Because the molecule they identified is not expressed in infants at the time they experience hypoxia, the researchers also plan to explore earlier developmental molecular targets.