Binge drinking in early adults can lead to long-lasting and potentially permanent dysregulation in the brain, according to a new study in mice, led by researchers at Penn State. They found that neurons, cells that transmit information in the brain via electrical and chemical signals, showed changes following binge drinking were similar in many ways to those seen with cognitive decline.
These findings, published in the journal Neurobiology of Aging, reveal that binge drinking early in life may have lasting impacts that are predictive of future health issues, like Alzheimer's disease and related dementias, the researchers said. The work could inform the development of therapeutics to help combat these changes - particularly in aging populations who may have given up alcohol decades earlier, according to Nikki Crowley, director of the Penn State Neuroscience Institute at University Park, Huck Early Career Chair in Neurobiology and Neural Engineering, assistant professor of biology in the Eberly College of Science, and the leader of the research team.
"We know from previous studies that there are immediate effects of binge drinking on the brain, but we didn't have any sense of if these changes were long-lasting, or reversible over time," said Crowley, who is also an assistant professor of biomedical engineering and of pharmacology. "We were interested in understanding if binge drinking during early adulthood may have lasting consequences that are not revealed until later in life - even if drinking had stopped for a very long period of time. This allows us to consider the effects of alcohol on an individual's holistic health, in terms of their entire life history."
In this study, the researchers placed mice on a voluntary binge alcohol drinking regimen that mimics a standard human binge drinker's exposure to alcohol. Mice were given access to alcohol every four days with abstinence in between - a pattern that parallels the way people tend to binge drink, with heavy drinking on the weekends followed by days off during the week. The mice were exposed to alcohol for a four-week period while they were 8 to 12 weeks of age, which approximates early adulthood - akin to someone in their early 20s - in humans. The mice were then not given any alcohol until 9 to 12 months of age, the equivalent of middle age, or late 30s to mid 40s, in humans.
"Because mice have a shorter lifespan than humans, but otherwise share a lot of their physiology, we can use them as a model to address important public health questions faster than we can in humans," Crowley said. "We can also perform experiments in a controlled laboratory setting that allow us to explore what is happening mechanistically at the cellular and molecular level, a depth that would not be possible in human studies. In this case, we can understand what alcohol is doing to the brain in isolation, without all the social stress and environmental factors that humans are dealing with."
After the break from alcohol, the researchers conducted electrophysiology studies to investigate the impact of binge drinking on the electrical properties of brain cells. The technique, called whole-cell patch-clamp electrophysiology, measures changes in two types of neurons - pyramidal and GABAergic - as well as changes in how signaling molecules, called neurotransmitters, talk to these neurons.
"Pyramidal neurons are excitatory neurons found throughout the brain, and heavily in the prefrontal cortex; they act like the gas pedal for the brain and encourage activity, whereas GABAergic neurons are inhibitory neurons that act like the brakes," Crowley said. "It's important for the gas and the brakes to be balanced and flexible to execute complicated cognitive tasks, and we know this balance can go awry for various reasons - including in neurodegenerative diseases like Alzheimer's disease and related dementias. We wanted to know if alcohol consumption could be a potential cause of that.
They found that effects of binge drinking in early adulthood were still present in the brain, even after a six-month abstinence-like period in the mice, with long-lasting changes in both pyramidal and GABAergic neurons.
"The intrinsic excitability, a proxy for how readily a neuron can talk to other neurons, of pyramidal neurons was changed so that it was harder for them to communicate," Crowley said. "We can think of this like how hard you need to press down on the gas pedal to get that car going; drinking alters this threshold so that more pressure is needed. It wasn't as easy for the pyramidal neurons to engage."
GABAergic neurons, however, experienced an increase in their excitatory drive. Glutamate - an important "go" neurotransmitter - more frequently signaled to GABAergic neurons, the researchers found. Similar changes in glutamate transmission, known as hyperexcitability, are seen during dementia-related cognitive decline, which Crowley said could indicate a potential link between alcohol consumption during early adulthood and changes in cognition during aging.
