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Scripps research scientists find clue to cause of childhood hydrocephalus
Date:9/7/2011

id fractions of blood, thus showing that bleeding events plausibly can lead to hydrocephalus by increasing the brain's exposure to LPA.

To investigate how LPA exerted this effect, the team produced mice that genetically lack one or both of the two receptorsLPA1 and LPA2to which LPA can bind on ventricle-building fetal progenitor cells, finding that the LPA1 receptor was required to produce hydrocephalus. "The idea here is that excess LPA causes these ventricular progenitor cells to get the wrong developmental signals via their LPA receptors, and so the ventricles and brain develop abnormally," said Chun.

In a final demonstration, the team pre-treated normal fetal mice with a compound that blocks the activation of LPA1 receptors, and found that even after LPA exposure, their signs of hydrocephalus were greatly reduced.

Looking Ahead

LPA1-blocking drugs currently are being developed for other conditions including lung fibrosis, and the new finding from Chun's lab may lead biotech or pharmaceutical companies to study their use in hydrocephalus. "If you had an unborn baby who was at risk from an injury to the mother, an infection, or evidence of bleeding then, in principle, you could treat with a short-acting LPA1 blocker to prevent or reduce hydrocephalus," said Chun.

The discovery that excess LPA can wreak havoc in the developing brain could have broader implications as well. Abnormally high concentrations of LPA may be generated by fetal brain cells themselves, also producing abnormal LPA signaling. Moreover, schizophrenia, autism, and other developmental brain disorders have also been linked to fetal bleeding events and infections as well as ventricular abnormalities.

"It's something that we need to investigate further," said Chun, "but it may be that excess LPA exposure in an unborn child's brain can have a variety of adverse effects on development, depending on the part of the brain that's exposed, the
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert  

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