The downside of a good defence

Many babies experience a temporary lack of oxygen during birth, and some children suffer long-lasting brain damage as a consequence. A study published online in Nature Neuroscience this week provides a potential explanation for this effect, by identifying a specific pathway by which low oxygen can disturb the development of an immature nervous system.

Although complete loss of oxygen rapidly kills nerve cells, which may explain some of the lasting damage, low oxygen levels are also known to switch on an evolutionarily ancient defensive mechanism in all cells. This mechanism is dependent on the transcription factor HIF-1. HIF-1 enhances anaerobic metabolism and blood vessel growth. But it is not known whether HIF-1 exerts any specific effects on nerve cells.

Roger Pocock and Oliver Hobert exposed pregnant roundworms to very low levels of oxygen, and then studied the nervous system in the offspring. They found very specific defects in the embryonic migration and axon growth of particular ? but not all ? nerve cells. Low oxygen increased expression of a receptor that is known to function in axon growth and migration, Vab-1. The specific nerve cell defects did not occur in mutant worms lacking either HIF-1 or Vab-1.

doi: 10.1038/nn.2152

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