A New Study Reveals the Significant Role of Brain Astrocytes in Controlling Circadian Rhythms

In a new study, researchers from the Molecular Biology Laboratory at the University of Cambridge Medical Research Council found that astrocytes, the nursecell cells that surround and support brain neurons, playing a more important role than previously understood in the circadian rhythm (the body's 24-hour circadian clock). Astrocytes were previously thought to be only neurons that support the regulation of circadian rhythms, but this new study suggests that they can actually guide the rhythm of this body clock and, for the first time, demonstrate that they can control the patterns of mammalian daily behavior. The related research result is published in the journal of Science.

When the circadian rhythm is disrupted, this can lead to jet lag and sleep disturbances, as well as a range of diseases ranging from mental illness to dementia, diabetes and cancer. The findings of this new study may guide the development of new treatments.

The circadian rhythm is widely known for its role in maintaining human health, and although many different types of cells in the body have been found to have their own internal clocks, however, the timing of these clocks is mainly controlled by the suprachiasmatic nucleus (SCN). The suprachiasmatic nucleus is a small brain region in the hypothalamus that acts as the master clock responsible for regulating daily behavior.

This new study utilizes microscopic imaging techniques to observe the detailed internal molecular clocking of astrocytes and neurons in SCN. Surprisingly, the results show that although both types of cells have their own circadian clocks, they are regulated differently and being observed to be active at different times of the day. They found that this subtle interaction is critical to keep the entire SCN clock running regularly.

After obtaining this initial discovery, the researchers found that the SCN function and behavior of the genetically engineered mice that silenced the body clock were disrupted. Unexpectedly, however, they found that recovering the genetic function of the astrocytes alone would allow these mice to regulate their daily activities, which means that even when astrocytes are the only cells in animals with functional in vivo circadian clocks, they still observe the daily pattern of behavior of the mice. When they compared this behavioral pattern to mice with a functional neuron clock, they found that the time of regulated activity in the SCN was shortened by about an hour, which is also reflected in the behavior of the mouse, indicating that astrocyte can control the behavior of animals to adapt to their own cellular characteristics.

The study also revealed glutamate as a chemical signal in the brain and central nervous system, which is used to transfer time clues of functional astrocytes in the SCN to a neuron partner without a clock rhythm. Dr. Marco Brancaccio, the first author of the paper, said, ‘To our great surprise, astrocytes are as efficient as neurons in producing a circadian clock signal in animals. We have learned from previous studies that these cells work in the circadian clock, but we didn't know at the time that they were able to restart the circadian rhythm of neurons. This adds a new and unexpected dimension to the neurobiology of the body clock, and offers some exciting ways for future research and development of therapeutic potential.’

Dr. Michael Hastings, author of the paper and author of the Molecular Biology Laboratory at the University of Cambridge Medical Research, added, ‘This is the first demonstration that astrocytes can actually control animal behavior. This is a major advance in the field of neuroscience.’