Overlooked brain cells could lead to new therapies for sleep disorders

Overlooked brain cells could lead to new therapies for sleep disorders
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Scientists have confirmed that astrocytes – a type of star-shaped brain cell – can have an impact on sleep.

A new study, carried out by researchers at UC San Francisco, has shown that astrocytes have an impact on how deep or how long sleep is. In the waking state, neurons in the brain are firing, which allows us to carry out our daily activities. However, when we sleep, the firing of the neurons meld to become a unified chorus of bursts, which neuroscientists call “slow-wave activity”, and the findings from this study suggest that astrocytes, not just neurons, help this happen.

The discovery could open new avenues for exploring sleep disorder therapies and could deepen our understanding of neurodegenerative diseases that are linked to sleep disturbances, such as Alzheimer’s disease.

The study has been published in the journal eLife.

Astrocytes

Astrocytes are a type of glial cell – a non-neuronal cell that maintains homeostasis in the body, as well as providing protection for neurons. They cover the brain with bush-like tendrils that allows each individual cell to monitor thousands of synapses – the points of communication between neurons – and connect to each other through specialised channels. Researchers think that it is these channels that allow astrocytes located at different points across the brain to act as one unified network.

This new study suggests that the hyperconnected astrocytes may be able to drive synchronised signalling in neurons, and that for some diseases in which sleep dysregulation is a factor, the disease is affecting astrocytes.

Trisha Vaidyanathan, the study’s first author and a neuroscience graduate student at UCSF, said: “This is the first example where someone did an acute and fast manipulation of astrocytes and showed that it was able to actually affect sleep. That positions astrocytes as an active player in sleep. It’s really exciting.”

In the study, author Kira Poskanzer, PhD, an assistant professor in the UCSF Department of Biochemistry and Biophysics, and team tracked changes in slow-wave activity in the brains of mice while manipulating astrocytes using a drug that can switch the cells on in genetically engineered animals. This led to the astrocytes firing up and, in turn, led to more slow-wave activity and sleep in the mice.

Depth and duration of sleep

To examine astrocytes’ role in more detail and discover how they exert their influence and what aspects of sleep they manage the team hijacked two receptor molecules – Gi and Gq receptors –that allow astrocytes to respond to signals coming from neurons and other types of cells around them.

The team discovered that each receptor molecule seemed to control a distinct aspect of sleep. The Gq receptors made animals sleep longer, but not more deeply, according to slow-wave measurements, while engaging Gi receptors put the mice into a much deeper slumber, without affecting sleep duration.

“Depth and duration are aspects of sleep that often get glossed over and lumped together even in neuroscience,” said Vaidyanathan. “But picking apart these different aspects and how they’re regulated is going to be important down the line for creating more specific sleep treatments.”

Affecting behaviour at a distant point

The team also found that astrocyte activity can trigger astrocytes in one part of the cortex to affect neuronal behaviour at a distant point. They are eager to look further into the extent of this influence and to continue to study how different astrocytic receptors work together to impact sleep.

Vaidyanathan said: “What have people been missing because they’re ignoring this group of cells? The questions that haven’t been answered thus far in sleep neurobiology – maybe they haven’t been answered because we haven’t been looking in the right places.”

“This could give us new insights not only into sleep but into diseases in which sleep dysregulation is a symptom,” added Poskanzer. “Maybe some diseases are affecting astrocytes in a way we hadn’t thought about before.”

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