Mild hypoxia in preterm infants linked to lifelong memory issues

During intensive care after preterm births, babies can experience low oxygen in their tissue and cells-or hypoxia. Hypoxia is linked to poor brain health outcomes and life-long memory issues, but the mechanisms are unclear. Researchers led by Art Riddle and Stephen Back, from Oregon Health and Science University, discovered a contributing mechanism by creating a mouse model for mild hypoxia following premature birth. Riddle emphasizes that, "The field has historically focused on how hypoxia injures white matter in the brain and kills neurons. This is the first study to explore how mild hypoxia may alter brain development without direct brain injury in this neonatal period." 

As presented in their JNeurosci paper, mild hypoxia shortly after birth hindered learning and memory into adulthood, and the researchers discovered, at least in part, the mechanism for this effect: altered neuron-to-neuron communication in the hippocampus. Probing a molecular mechanism, the researchers found that hypoxia following premature birth affected a protein channel involved in neuron-to-neuron communication and memory that develops in the hippocampus during adolescence. They also identified a second protein that was involved in hypoxia's effects on the channel's functioning. When the researchers targeted this second protein in adult mice, they restored the channel's function. Adds Riddle, "We also found that this protein was altered by mild hypoxia when we looked at surrounding brain areas, which suggests other brain regions may also be susceptible to hypoxia." 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 preterm babies influences neuron communication in memory-related brain regions to hinder learning and memory into adulthood. Speaking on clinical implications, says Riddle, "The subtle deficits from mild hypoxia that we studied here are commonly seen in clinical settings with preterm babies." Because the molecule they identified is not expressed in babies at the time that they experience hypoxia, the researchers also plan to explore earlier developmental molecular targets.