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LIQUOR DEATH
Scientists have cracked the mystery
of brain damage caused by alcohol, reports Biplab Das
Seven-year-old Barun used to find it difficult to recollect what he had learnt. When he was taken to a doctor, it was discovered that he owed his problems to the fact that his mother had been an alcoholic during pregnancy.
Scientists have known for long that alcohol damages a developing brain. But how it does this has remained a mystery. Neuroscientist John Onley of Washington University and paediatric neurologist, Chrysanthy Ikonomidou of Humboldt University, Berlin, report in
Science that alcohol reaches two of the brain's neurotransmitters, glutamate and GABA (gamma aminobutyric acid), via receptors to kill neurons in baby rats.
Onley and his colleagues exposed two-week-old animals to high doses of alcohol. At this stage the rat's brain goes through developmental
stages which take place in the human brain during the last phase of pregnancy. Earlier studies had shown that ethanol blocks NMDA
(N-methyl-D-aspartate) receptors for glutamate and activates GABA receptors. "It provides the first step to understanding how you might control that damage," said pharmacologist Boris Taba Koff of the University of Colorado Health Sciences Centre in Denver.
Last year, the research team stumbled upon some chemicals, which, by blocking NMDA receptors for glutamate, cause a benign neuron death called apoptosis (programmed cell death). Moreover, the chemicals excite receptors for
GABA, resulting in similar neuron death. This happens when neurons in a developing brain are painstakingly making connections with each other.
Looking for drug-induced neuronal death, the research team isolated two candidates, barbiturates and
benzodiazepines. Both drugs silence neurons, arousing the receptors for the inhibitory neurotransmitter,
GABA. This also causes programmed death of neurons.
"This insight into the alcohol-mediated death zone shows that late pregnancy drinking is really unsafe for the developing brain," said David Longer, a neurobiologist at
Vanderbilt University School of Medicine in Nashville, Tennessee, US. Other groups also found evidence that implicates NMDA receptors. For instance, pharmacologist Paula Hoffman of the University of Colorado Health Sciences Centre and her teammates showed that blocking NMDA receptors kills neurons in the rat's cerebellum. But her new findings show that neurons from other regions also died. "What's more, the involvement of GABA receptors in the killing spree of alcohol is quite novel," says Hoffman.
These results also cast doubts on the role of benzodiazepines, which are given to newborns as
anti-convulsants. This drug might also be responsible for neuronal death in the brains of human infants. "However, rats were given higher doses of
benzodiazepines than those usually given to infants, and further studies are needed to prove that infants are at risk from this drug," pointed out
Ikonomidou. She added that it could cause irreversible damage in infants. "But the tragedy is that we do not have good alternative drugs to use," she lamented.
This crisis might be overcome by Onley and his group's work, which will open avenues for new drugs, which can block alcohol's harmful effects in pregnant women.
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