Dr. Ted Abel, a University of Pennsylvania professor of biology, led the research team to better understand the role of nucleoside adenosine in the hippocampus, the part of the brain associated with memory function.
The research is published in The Journal of Neuroscience.
“For a long time, researchers have known that sleep deprivation results in increased levels of adenosine in the brain, and has this effect from fruit flies to mice to humans,” Abel said.
“There is accumulating evidence that this adenosine is really the source of a number of the deficits and impact of sleep deprivation, including memory loss and attention deficits. One thing that underscores that evidence is that caffeine is a drug that blocks the effects of adenosine, so we sometimes refer to this as ‘the Starbucks experiment.'”
Abel’s research actually involved two parallel experiments on sleep-deprived mice, designed to test adenosine’s involvement in memory impairment in different ways.
One experiment involved genetically engineered mice that could not produce the adenosine researchers believe might cause the cognitive effects associated with sleep deprivation.
The other experiment involved a pharmacological approach. The researchers grafted a pump into the brains of mice that hadn’t been genetically engineered; the pump delivered a drug that blocked a particular adenosine receptor in the hippocampus.
If the receptor was indeed involved in memory impairment, sleep-deprived mice would behave as if the additional adenosine in their brains was not there.
To see whether these mice showed the effects of sleep deprivation, the researchers used an object recognition test. On the first day, mice were placed in a box with two objects and were allowed to explore them while being videotaped.
Both sets of treated mice explored the moved object as if they had received a full night’s sleep. “These mice don’t realize they’re sleep-deprived,” Abel said.
Abel and his colleagues also examined the hippocampi of the mice, using electrical current to measure their synaptic plasticity, or how strong and resilient their memory-forming synapses were. The pharmacologically and genetically protected mice showed greater synaptic plasticity after being sleep deprived than the untreated group.
Combined, the two experiments cover both halves of the chemical pathway involved in sleep deprivation.
The knowledge that interrupting the pathway at either end results in mice that show no memory impairments is a major step forward in understanding how to manage those impairments in humans.
“To be able to reverse a particular aspect of sleep-deprivation, such as its effect on memory storage, we really want to understand the molecular pathways and targets,” Abel said.
“Here, we’ve identified the molecule, the cellular circuit and the brain region by which sleep deprivation affects memory storage.”
Such treatments would be especially enticing, given how sensitive the brain is to sleep deprivation’s effects.
“Our sleep deprivation experiments are the equivalent of losing half of a night’s sleep for a single night,” Abel said. “Most of us would think that’s pretty minor, but it shows just how critical the need for sleep is for things like cognition.”
Source: University of Pennsylvania