Scientists have identified a signaling molecule that plays a mediating role in the damage of fetal brains due to a lack of oxygen. They say that this is a step towards preventing such brain damage, which can lead to a variety of physical and mental problems including mental retardation, epilepsy, schizophrenia, autism and cerebral palsy.
There are many possible causes of hypoxia, including smoking, exposure to smoke and carbon monoxide, disruption of blood flow, choking, diseases causing paralysis of the breathing muscles such as amyotrophic lateral sclerosis (ALS), high altitudes, pressure on the windpipe, strangulation and physical injuries, cardiac arrests and drug overdose. Now, researchers have identified a signaling molecule that is involved in this damage, moving closer towards the prevention of the problem.The phospholipid molecule lysophosphatidic acid (LPA) acts as a signal for the formation of new neurons in fetal brains. At the same time, it also signals the fetal brain damage that results from hypoxia. Lead researcher and Scripps Research Professor Jerold Chun, MD, PhD, said in a press release: "Fetal brain damage from oxygen deprivation involves specific changes that are, surprisingly, mediated by this lipid signal called LPA."
Discovering this, Professor Chun explained that this mediation pathway can be controlled with drugs, and "the discovery suggests that creating new medicines that target LPA receptors may be a way of limiting or preventing serious developmental brain diseases."
Focusing on the development of young neurons in the cerebral cortex of fetal mouse brains and brains grown in petri dishes, the researchers discovered that hypoxia resulted in the overstimulation of the neurons, making them behave in the same way they do when they are exposed to too much LPA.
This was a surprise for the scientists because they had taken for granted that brain damage caused by hypoxia involved the random destruction and death of neurons. However, the research shows that hypoxia damages developing cerebral cortical neurons in a very specific way, and that the way involves LPA signaling.
The researchers explained that this information could lead to a strategy to target and block hypoxia-caused brain-development damage for which there is currently no treatment. This would be a welcome addition to public health efforts to prevent hypoxia-caused fetal brain damage such as warning pregnant women not to smoke. Other steps to prevention are avoiding risks and triggers of the known causes such as drugs.
The article, "Stereotyped fetal brain disorganization is induced by hypoxia and requires lysophosphatidic acid receptor 1 (LPA ) signaling," (doi: 10.1073/pnas.1106129108) by Keira Joann Herr, Deron R. Herr, Chang-Wook Lee, Kyoko Noguchi, and Jerold Chun appears in the journal PNAS.
Top Photo: Professor Jerold Chun, MD, PhD, © Scripps Research Institute