Researchers from Tufts University determined star-shaped brain cells, called astrocytes, may be responsible for the rapid improvement in mood in depressed patients after acute sleep deprivation.
The study, published in the current issue of Translational Psychiatry, explains how astrocytes regulate a neurotransmitter involved in sleep.
Investigators believe the findings may lead to the development of effective and fast-acting drugs to treat depression, particularly in psychiatric emergencies.
Current drugs used to treat depression often take weeks to work effectively. Sleep deprivation, however, has been shown to be effective immediately in approximately 60 percent of patients with major depressive disorders.
Although widely recognized as helpful, it is not always ideal because it can be uncomfortable for patients, and the effects are not long-lasting.
During the 1970s, research verified the effectiveness of acute sleep deprivation for treating depression, particularly deprivation of rapid eye movement sleep, but the underlying brain mechanisms were not known.
Most of what we understand of the brain has come from research on neurons, but another type of largely ignored cell, called glia, are their partners.
Although historically thought of as a support cell for neurons, researchers found that a type of glia, called astrocytes, affect behavior.
The researchers with Dr. Phil Haydon’s group at Tufts University School of Medicine, had established previously that astrocytes regulate responses to sleep deprivation by releasing neurotransmitters that regulate neurons.
This regulation of neuronal activity affects the sleep-wake cycle. Specifically, astrocytes act on adenosine receptors on neurons. Adenosine is a chemical known to have sleep-inducing effects.
During our waking hours, adenosine accumulates and increases the urge to sleep, known as sleep pressure. Chemicals such as caffeine are adenosine receptor antagonists and promote wakefulness. In contrast, an adenosine receptor agonist creates sleepiness.
“In this study, we administered three doses of an adenosine receptor agonist to mice over the course of a night that caused the equivalent of sleep deprivation.
“The mice slept as normal, but the sleep did not reduce adenosine levels sufficiently, mimicking the effects of sleep deprivation. After only 12 hours, we observed that mice had decreased depressive-like symptoms and increased levels of adenosine in the brain, and these results were sustained for 48 hours,” said first author Dustin Hines, Ph.D.
“By manipulating astrocytes we were able to mimic the effects of sleep deprivation on depressive-like symptoms, causing a rapid and sustained improvement in behavior,” continued Hines.
“Further understanding of astrocytic signaling and the role of adenosine is important for research and development of antidepressant drugs. Potentially, new drugs that target this mechanism may provide rapid relief for psychiatric emergencies, as well as long-term alleviation of chronic depressive symptoms,” said Naomi Rosenberg, Ph.D., dean of the Sackler School of Graduate Biomedical Sciences and vice dean for research at Tufts University School of Medicine.
“The team’s next step is to further understand the other receptors in this system and see if they, too, can be affected.”