Understanding neuron-glia crosstalk and biological clocks in insomnia

According to the World Health Organization, about one-third of the population experiences insomnia symptoms, and about 10–15% suffer from chronic insomnia, the most common sleep disorder. Sleeping difficulties associated with insomnia are often linked to chronic sleep deprivation, which has a negative health impact partly due to disruption in the internal synchronisation of biological clocks. These are regulated by clock genes and modulate most biological processes. Most studies addressing circadian rhythm regulation have focused on the role of neurons, yet glial cells also impact circadian rhythms and sleep regulation. Chronic insomnia and sleep loss have been associated with glial cell activation, exacerbated neuroinflammation, oxidative stress, altered neuronal metabolism and synaptic plasticity, accelerated age-related processes and decreased lifespan. It is, therefore, essential to highlight the importance of glia–neuron interplay on sleep/circadian regulation and overall healthy brain function. Hence, in this review, we aim to address the main neurobiological mechanisms involved in neuron-glia crosstalk, with an emphasis on microglia and astrocytes, in both healthy sleep, chronic sleep deprivation and chronic insomnia.