Mouse study identifies protective mechanism against alcohol-induced embryo toxicity
Researchers have identified a mechanism by which the eight amino acid peptide NAP, an active fragment of a neuroprotective brain protein, protects against alcohol-induced embryo toxicity and growth retardation in mice. Their findings bring alcohol researchers a critical step closer to developing pharmacologic agents to prevent alcohol-induced fetal damage. The study, funded by the National Institutes of Healths National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Child Health and Human Development (NICHD), and the Medical Research Service, Department of Veterans Affairs, appears in the current issue of the Proceedings of the National Academy of Sciences.*
The researchers produced NAP derivatives with specific substitutions and screened the compounds in cultured rat neurons for their protection against cell toxins and in whole mouse embryos for their protection against alcohol. By manipulating NAPs structure and thereby altering its activity, the researchers were able to examine the ability of the different NAP derivatives to block alcohol inhibition of the L1 cell adhesion molecule. Their results indicate that NAP protects mouse embryos from alcohol toxicity by blocking alcohol effects on L1 rather than by its broad neuroprotective actions.
“This elegant study demonstrates that the protective effect of NAP against alcohol damage differs from that of NAP against neurotoxins, said Ting-Kai Li, M.D., Director, National Institute on Alcohol Abuse and Alcoholism. “Ethanol inhibition of L1 is now strongly implicated in the pathogenesis of fetal alcohol damage and a foremost target of medication development.”
Michael Charness, M.D., of the Veterans Administration Boston Healthcare System and Department of Neurology, Harvard Medical School, headed up the study, with colleagues from the NICHD and the University of North Carolina Bowles Center for Alcohol Studies.
NAP, technically known as NAPVSIPQ, is known to be protective in minute concentrations against a wide array of neural insults and recently was shown to prevent alcohol-induced fetal wastage and growth deficits in mice. In September 2002, Dr. Charness with other colleagues reported that NAP also blocks alcohols inhibitory effects on cell-cell aggregation (the clustering of fetal cells destined to become the brain and nervous system) as mediated by the cell adhesion molecule known as L1. Whether NAPs broader neuroprotective action or its specific effects on cell adhesion were responsible for preventing fetal damage remained to be determined.
The leading preventable cause of mental retardation in the United States, fetal alcohol syndrome affects about 1 in 1,000 U.S. infants and about 6 percent of children born to alcoholic women. Fetal alcohol syndrome imposes lifetime economic costs estimated at $1.8 million per child in health care and indirect costs such as lost productivity.
Alle Nachrichten aus der Kategorie: Health and Medicine
This subject area encompasses research and studies in the field of human medicine.
Among the wide-ranging list of topics covered here are anesthesiology, anatomy, surgery, human genetics, hygiene and environmental medicine, internal medicine, neurology, pharmacology, physiology, urology and dental medicine.
Material found in house paint may spur technology revolution
Sandia developed new device to more efficiently process information. The development of a new method to make non-volatile computer memory may have unlocked a problem that has been holding back…
Immune protein orchestrates daily rhythm of squid-bacteria symbiotic relationship
Nearly every organism hosts a collection of symbiotic microbes–a microbiome. It is now recognized that microbiomes are major drivers of health in all animals, including humans, and that these symbiotic…