Recent research in mice indicates that destructive activity of cells in the brain is increased after sleep deprivation and may increase the risk of developing dementia, such as Alzheimer's disease.
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To maintain healthy brain connections, it is important that debris is cleared away so electric impulses can be transferred smoothly between neurons. This role is carried out by the brain's glial cells. Research published this week reports that lack of sleep can accelerate the activity of glial cells, increasing the risk that they also destroy healthy cells. The authors propose that it may be such destructive activity that increases the risk of developing Alzheimer’s disease and other neurological disorders.
Michele Bellesi of the Marche Polytechnic University in Italy compared the brains of mice who had slept well with those of mice who had been kept awake for one night and with mice who were kept awake five nights in a row. In particular they studied the activity of two keys types of glial cells—astrocytes and microglial cells—that have previously been shown to have increased activity after sleep deprivation.
Astrocytes provide a wide range of important tasks within the brain, including axon guidance and synaptic support and control of the blood brain barrier. They tidy up unnecessary synapses allowing changes in the wiring of the brain to occur.
Phagocytosis of presynaptic components by astrocytes was shown to be elevated after both acute and chronic sleep loss compared with normal sleep-wake patterns. Astrocyte activity was observed in more than twice as many synapses in mice who were chronically sleep-deprived compared with the mice who were well rested. Sleep deprivation therefore resulted in the astrocytes breaking down more of the brain’s connections and their debris, but it has yet to be determined whether or not this activity is beneficial. Since the additional activity was seen at the largest, most mature synapses, it may be that these synapses were in need of additional cleaning and that this is highlighted in a state of sleep deprivation.
We show for the first time that portions of synapses are literally eaten by astrocytes because of sleep loss”.
Michele Bellesi, Marche Polytechnic University
Microglial cells are important for learning and memory. They keep the brain free from damaged cells and debris, oversee the growth of new neurons and cultivate new connections to keep the mind fertile and flexible. Bellesi found that the activity of these cells was also increased in the mice who suffered chronic sleep deprivation compared with those who has slept normally. This is a more worrying observation since excessive microglia activity can make the brain more vulnerable to further damage.
Bellesi explained “We already know that sustained microglial activation has been observed in Alzheimer’s and other forms of neurodegeneration”.
Further research is required to evaluate the impact of this increase in glial cell activity after sleep loss and to assess whether the effects can be reversed by quality sleep. However, this finding may explain why people with chronic sleep deprivation are more susceptible to developing dementias.
- Bellesi M, et al. Sleep Loss Promotes Astrocytic Phagocytosis and Microglial Activation in Mouse Cerebral Cortexet. Journal of Neuroscience 2017. Epub ahead of print. al Available at: http://www.jneurosci.org/content/37/21/5263