by Leslie H. Lang
November 06, 2004
The UNC findings, from research at UNC's Bowles Center for Alcohol Studies, were based on an animal model of chronic alcohol dependence, in which adult rats were given alcohol over four days in amounts that produced alcohol dependency. The study is in the Nov. 3 issue of the Journal of Neuroscience.
In 2002, Dr. Fulton T. Crews, Bowles Center director, and Bowles Center research associate Dr. Kim Nixon were the first to report that alcohol, during intoxication, has a detrimental effect on the formation of new neurons in the adult rat hippocampus. This brain region is important for learning and memory - in animals and humans - and is linked to psychiatric disorders, particularly depression.
"When used in excess, alcohol damages brain structure and function. Alcoholics have impairments in the ability to reason, plan or remember," said Crews, also professor of pharmacology and psychiatry in UNC's School of Medicine. "A variety of psychological tests show alcoholics have a difficulty in ability to understand negative consequences."
In the new study, senior co-author Crews and co-author Nixon found inhibition of neurogenesis, or brain cell development, during alcohol dependency, followed by a pronounced increase in new neuron formation in the hippocampus within four-to-five weeks of abstinence. This included a twofold burst in brain cell proliferation at day seven of abstinence.
"We looked at dividing cells after our four-day binge model of alcohol dependency and confirmed what we previously observed: When the animals were intoxicated, the measure of dividing cells decreases," said Nixon. "And after abstinence for one week, we saw a huge burst in the number of new cells being born."
Nixon said the findings were confirmed by use of several biological markers, including bromodeoxyuridine, BrdU. Animals were injected with BrdU, which labels dividing cells. BrdU inserts itself into the DNA of a cell during cell division, so that it's found only in cells that have divided during the two hours that the substance is in the animals' system.
Imaging studies report shrinkage in brain ventricles - the fluid-filled spaces within the brain - indicating that the brain is growing as the spaces shrink as alcoholics recover from alcohol dependence.
"And when they stop drinking, you can show in a period of weeks, months, years, the brain grows back, there's a return of metabolic activity, and cognitive tests show a return of function," Crews said.
The findings may have significant implications for treatment of alcoholism during recovery. The discovery of regeneration of neurons in recovery opens up new avenues of therapies aimed at regeneration of brain cells. "When animals learn, they make more neurons. When animals exercise, they make more neurons and learn faster, as well," Crews said.
"Pharmacological agents such as antidepressants and behaviors such as running, increased physical activity and learning experiences apparently help regulate the process of neurogenesis," he added. "Our research suggests they could be considered in the treatment of chronic alcohol dependency."
In their report, Nixon and Crews also said that their findings for the first time provide a neuronal regeneration mechanism that may underlie the return of normal cognitive function and brain volume associated with recovery from addiction during abstinence from alcohol.
"This is really the first biological measure of a major change in neuronal structure consistent with changes that are known to occur when individuals are able to stop drinking," said Crews.
For decades, neuroscientists believed the number of new cells, or neurons, in the adult brain was fixed early in life. Adaptive processes such as learning, memory and mood were thought tied to changes in synapses, connections between neurons.
More recently, studies have shown that the adult human brain is capable of producing new brain cells throughout life, a neurogenesis resulting in formation of hundreds of thousands of new neurons each month. "Prior to our work, everyone merely assumed that glia, the supporting cells of the brain, regenerated or that existing brain cells altered their connections," said Nixon. "We have shown a burst in new cell birth that may be part of the brain's recovery after the cessation of alcohol."
Chronic alcoholism, a disease affecting more than 8 percent of the adult U.S. population, or more than 17 million Americans, produces cognitive impairments and decreased brain volumes, both of which are partially reversed during abstinence.
Alcohol dependence also is associated with depression, which is consistent with inhibition of neurogenesis. Cessation from alcohol is associated with improved cognitive abilities, Crews said.
Note: The research was supported by the National Institute on Alcohol Abuse and Alcoholism, the Alcoholic Beverage Medical Research Foundation and UNC's Bowles Center.
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