Astrocytes regulate sleep pressure and memory deficits associated with sleep deprivation

Scientists have discovered an unexpected brain mechanism that modulates the regulation of sleep and the consequences of sleep deprivation. The research, published by Cell Press in the January 29th issue of the journal Neuron, opens new avenues for development of treatments for disorders and cognitive deficits associated with sleep loss. Glial cells are brain cells that do not transmit nerve impulses the way that neurons do. Astrocytes are a type of glial cell that play multiple supportive roles and modulate signaling around neurons. Astrocytes can release chemical transmitters that influence synaptic activity through a process called gliotransmission. Senior study author Dr. Philip G. Haydon from Tufts University School of Medicine and his colleagues had previously shown that astrocytes release ATP and regulate extracellular adenosine that acts on synaptic A1 receptors.

Although it has been established that adenosine is a transmitter involved in the drive for sleep following prolonged wakefulness, the cellular source and mechanisms of action of adenosine in the process of sleep are not well understood. Dr. Haydon and colleagues used astrocyte-specific transgenic mice to explore the role of astrocytes and adenosine in the regulation of sleep. Using their transgenic model, they could selectively and reversibly interfere with gliotransmission.

The researchers found that genetic inhibition of neurotransmitter release from astrocytes reversibly decreased the accumulation of sleep pressure after sleep deprivation and prevented cognitive deficits associated with sleep loss. Further, the A1 antagonist CPT failed to suppress sleep following inhibition of gliotransmission, and administration of CPT in control animals was protective against the memory-degrading effects of sleep deprivation.

" Taken together these studies provide the first demonstration that a nonneuronal cell type in the brain, the astrocyte, modulates behavior and provides strong evidence of the important role of A1 receptors in the regulation of sleep and the cognitive decline associated with sleep loss," explains Dr. Haydon. "Given that astrocytes express novel receptors; these glial cells may offer a distinct target for the development of therapeutics for sleep and cognitive disorders."

Source: Cell Press