Paper of the Month: Brains shrink in monkeys that drink
This month's featured paper is from Drs. Kroenke and Grant, working with researchers at Stanford University and SRI International, and is titled, "Monkeys that Voluntarily and Chronically Drink Alcohol Damage their Brains: A Longitudinal MRI Study." It was published in the journal Neuropsychopharmacology.
Monkeys that Voluntarily and Chronically Drink Alcohol Damage their Brains: A Longitudinal MRI Study
Major progress to address the first of these questions was made almost 25 years ago when Adolph Pfefferbaum, M.D., Edith Sullivan, Ph.D., and their co-workers at Stanford University and SRI International used non-invasive magnetic resonance imaging (MRI) measurements to document that the brains of alcoholics are smaller than age-matched controls. Studies of recovering alcoholics performed by multiple researchers have subsequently shown that brain volume differences fade away with abstinence from drinking. However, further progress understanding the amount of alcohol exposure necessary to affect brain volume, or the biological mechanism underlying these tissue changes has been difficult - mainly due to technical and ethical limitations inherent in human studies.
"For example, it is not possible to stringently control, or even quantify, the amount a person drinks in a long-term study," remarked Christopher Kroenke, Ph.D., assistant professor of behavioral neuroscience and associate scientist at the Advanced Imaging Research Center. Dr. Kroenke is the first author of this month's groundbreaking paper of the month. "Even more complex is the long list of potentially confounding issues present in human studies, such as other substance abuse, nutritional factors, and biases associated with recruiting human subjects for study."
The paper, titled, "Monkeys that Voluntarily and Chronically Drink Alcohol Damage their Brains: A Longitudinal MRI Study" (published in the journal Neuropsychopharmacology) confronts this obstacle by conducting an MRI study of brain changes in nonhuman primate subjects.
Kathleen Grant, Ph.D., professor of behavioral neuroscience, senior scientist and head of the Division of Neuroscience at the Oregon National Primate Research Center, and an investigator in the study, had previously documented how individual rhesus monkeys, just like humans, voluntarily drink consistent amounts of alcohol. "Interestingly, another similarity to human drinking behavior is that a wide range is observed, with some monkeys drinking a lot of alcohol, while others drink very little," she said.
For this study Dr. Grant teamed with Dr. Kroenke, who heads the ONPRC MRI support core. In a collaborative effort with Drs. Pfefferbaum and Sullivan, the researchers characterized brain volume changes with drinking in 18 monkeys over a 1 year course of voluntary drinking. "Indeed, in these monkeys, brain volume reductions were observed with drinking, particularly within cerebral cortical gray matter," said Dr. Kroenke. He explained that "due to the ability to record the amount of alcohol consumed, it was possible to determine that the volume change was proportional to the amount of alcohol consumed. About 0.1% of the total brain volume is lost from the cerebral cortex per daily drink (averaged over the course of a year)."
These findings affirm conclusions from studies of human subjects on the role of alcohol in brain volume shrinkage. A notable difference from studies of human alcoholics (who typically drink heavily for decades prior to study) was the lack of volume changes in the nonhuman primate white matter. This difference buttresses previous suggestions that cerebral cortical gray matter changes take place first, and white matter is less sensitive to alcohol exposure.
This work opens several potential new directions. Within this group of 18 monkeys, only two drank on average less than 4 drinks per day. It would be of great interest to determine whether lower levels of drinking are also characterized by the 0.1% per daily drink relationship. Future and more elaborate MRI studies using diffusion tensor imaging are also planned to determine whether cellular-level changes in white matter are apparent in drinking monkeys prior to macroscopic white matter volume reductions. Importantly, due to the existence of this animal model of alcoholism, all of these future efforts can now be followed up with traditional anatomical techniques to investigate the mechanistic link between alcohol exposure and brain volume changes.
Drs. Kroenke, Grant and team will continue to advance our understanding of the complex relationship between alcohol and the brain.
About the Paper of the Month
The School of Medicine newsletter spotlights a recently published faculty research paper in each issue. The goals are to highlight the great research happening at OHSU and to share this information across departments, institutes and disciplines. The monthly paper summary is selected by Associate Dean for Basic Science Mary Stenzel-Poore, Ph.D., and Associate Dean for Clinical Science Eric Orwoll, M.D.
More Published Papers
The entire list of OHSU papers published this month is here.
The Paper of the Month article is written by Jackie Wirz, Ph.D.