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Examining brain damage that occurs when fetuses in the womb aredeprived of oxygen, researchers at The Scripps Research Institutehave discovered that damage does not occur randomly but is linkedto the specific action of a naturally occurring fatty moleculecalled LPA, acting through a receptor that transfers informationinto young brain cells. This observation made in mice suggests that LPA may also be linkedto the damage caused by oxygen deprivation in human fetuses. Ifthat proves to be the case, the research may help scientists andphysicians better understand and find new ways to address thenumerous developmental disorders that can arise when fetuses aredeprived of oxygen in the womb-including mental retardation, epilepsy , schizophrenia , autism , cerebral palsy and a range of other physical and mental problems. "Fetal brain damage from oxygen deprivation involves specificchanges that are, surprisingly, mediated by this lipid signalcalled LPA," said Scripps Research Professor Jerold Chun, MD, PhD,a member of the Dorris Neuroscience Center who led the research,which appeared in an advance, online issue of the journalProceedings of the National Academy of Sciences (PNAS) this week. "Because this pathway can be targeted with drugs," he added, "thediscovery suggests that creating new medicines that target LPAreceptors may be a way of limiting or preventing seriousdevelopmental brain diseases." Currently, there is no way to treat the neurological damageproduced by oxygen deprivation. How Lack of Oxygen Affects the Fetal Brain A developing fetus might be temporarily deprived of oxygen-acondition known as "hypoxia"-for any number of reasons, includingdisruption of blood flow, exposure to smoke, carbon monoxide, orphysical trauma. Physicians have long known that hypoxia can lead to brain damageand increased risk of developmental disorders, and existing publichealth efforts are aimed at mitigating these risks. Awareness thatcarbon monoxide from cigarettes can cause hypoxia, for instance, isthe major reason why women are warned not to smoke when they arepregnant. Still, there is a need to find other ways to address the problem,since not every situation in which fetuses might be subjected tooxygen deprivation is preventable. The discovery by Chun, graduatestudent Keira Herr, and colleagues suggests that there may be a wayto mitigate the damage caused by hypoxia directly, by drugstargeting the molecules in the brain that mediates thisdamage-specifically, the receptor for the phospholipid moleculelysophosphatidic acid (LPA). Phospholipids, molecules of fat with a charged head on one end, areuniversally found in biological organisms because they are anessential building block of cellular membranes, defining theboundaries of cells and keeping things inside a cell separated fromthat which is outside. But lipids do more than just form barriers. LPA acts as a signal toaffect the development of mammalian brains-something that Chun andhis colleagues first demonstrated several years ago. His laboratoryidentified the first cellular receptor to which LPA binds, and theydiscovered that LPA acts as a signal that influences neurogenesis,the formation of new neurons when fetal brains are developing inthe womb, along with the architecture of the brain. As the brain grows in developing fetuses, it forms specializedregions very quickly. Many of these regions must be up and runningby the time a baby is born. Newborns need to be able to breathe,drink, digest, respond to stimuli, and function in countless otherbasic ways in order to survive. Problems that arise as the early brain develops may lead todevelopmental disorders. Findings that Provide a New Strategy to Block Damage The prominent role LPA plays in fetal brain development is what ledChun and his colleagues to investigate whether it also played arole in developmental disorders, many of which are believed to belinked to brain disorganization that arises during earlydevelopment as has been documented in the clinical literaturefollowing hypoxic insults. The team studied the effect of hypoxia in the brains of developingmice and also on brains temporarily grown in Petri dishes. Inparticular, the researchers studied the changes that occur in youngneurons of the cerebral cortex, the part of the brain believed tobe involved in higher functions, like memory, cognition, reasoning,and the interpretation of sensory input. Chun and his colleagues discovered that when hypoxia damagesdeveloping cerebral cortical neurons, it does so in very specificways that require LPA signaling. Scientists had long assumed thatthe association between hypoxia and brain damage was a non-specificone in which individual neurons all over the brain were randomlykilled as a result of being deprived of oxygen. What Chun and his colleagues found, however, is that hypoxia causesthe neurons to become overstimulated, mimicking effects produced byexcessive LPA exposure. Genetically removing the receptors for LPAor blocking them through drugs stopped these effects. Knowing that hypoxia causes brain damage through this LPA signalingpathway provides a strategy to target and block that damage.Blocking LPA signaling may be a new way to prevent damaging changesto the brain and attenuate or prevent diseases linked to hypoxia, aconcept that awaits further testing in humans. The article, "Stereotyped fetal brain disorganization is induced byhypoxia 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 Chunappears in the journal PNAS. See: This work was funded primarily by the National Institutes ofHealth, with fellowship support by the Agency of Science,Technology and Research, Singapore. Additional References Citations. The e-commerce company in China offers quality products such as China Moving Heads Lighting , Laser Beam Lighting Manufacturer, and more. For more , please visit Led Par Can Lights today!
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