Eunomica Blog: Just in case, Do the right thing: Take a nap!

La malattia di Alzheimer è la forma più comune di demenza senile, una patologia progressiva ed irreversibile che colpisce il cervello e per la quale a tutt’oggi non ci sono cure. Il morbo di Alzheimer comporta la perdita di funzioni cognitive, dato che colpisce aree del cervello implicate nella memoria, nel linguaggio e nell’elaborazione dei pensieri.

Dati sempre più consistenti stanno portando alla luce l’importanza del sonno, non solo come momento necessario a ristabilire le funzioni vegetative di base e a immagazzinare le informazioni acquisite durante la giornata, ma anche come momento indispensabile al cervello per “fare pulizia”, ovvero eliminare i metaboliti di scarto accumulati durante l’intera giornata.

Why is sleeping so important?

Our body carries out many different functions, whose roles are well known, but understanding why we spend a third of our lives sleeping is less intuitive.

Sleeping is necessary to vital functions, since the long-term effects of sleep deprivation lead to death rodents and flies within a short period of time.

Moreover, by sleeping we restore vegetative functions as well as we elaborate information experienced during the day.

A new study, by Maiken Nedergaard and colleagues at the University of Rochester in New York, provides a better understanding on the role of sleep: by sleeping the brain clears out toxic peptides.

Alzheimer disease (AD) is the most common form of dementia and one of the major pathological hallmarks of the disease is the formation of extracellular amyloid plaques, which are abnormal aggregates of the amyloid-β peptide (Aβ). Aβ is aggregation prone, and, by aggregating, it forms deposits that may surround brain cells.

On the way torward the formation of amyloid plaques, transient forms of aggregated Aβ cause biochemical changes within the cells that culminate in the impairment of synaptic functions.

It seems then that the brain needs to clear out this peptide, especially when the equilibrium that controls the level of Aβ is mysregulated in favour of its accumulation.

One of the mechanism foresees to clear Aβ via the cerebrospinal fluid (CSF). The CSF is a fluid that circulates in the brain and interchanges with the interstitial fluid (the blood), so that all the molecules that enter the CSF can diffuse into the blood stream.

On the other way around, molecules within the interstitial fluid can diffuse in the CSF and exert their effect on brain cells, but this process is under the tight control of the blood brain barrier, an interface that keeps separated the brain from the circulatory system.

The CSF is a sort of “lymphatic” system, which flush out metabolic waste, since the brain is the only organ in the human body that lacks a clearance system as the lymphatic one.

Nedergaard and coll have used the in vivo two-photon imaging technique, which can reveal dye molecules in living cells, to compare the circulating CSF into the cortex of awake and sleeping mice. They injected labeled Aβ and found out that during sleep CSF cleared away this toxic peptide twofold faster than in awake mice, mainly because during sleep it is increased the efflux from the CSF toward the interstitial fluid.

The main point of this study is that sleep deprivation may have a correlation with the onset of neurological disorders, by preventing the brain from removing toxic metabolites.

Can sleeplessness become an alarm bell for neurological dysfunctions?

Emerging data reveal that the build-up of amyloid plaques is favoured by poor sleep.

Brain metabolism and activity pivot the production of end products that need to be removed, so sleep seems to be necessary to the brain to “clean” itself.

Investigating the importance of sleep is becoming very attractive in neuroscience, since other neurodegenerative disorders, such as Parkinson’s disease or chronic traumatic encephalopathy, are also associated with the accumulation of toxic peptides within the brain. To clarify the aspects underlying the real importance of better sleep will require further investigations and efforts, but, in the meantime, it could be a good strategy to keep the brain “in trim” in order to prevent the onset of neurological disorders.

Bibliography

Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O'Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M (2013) Sleep drives metabolite clearance from the adult brain. Science 342: 373-377.

Livia Civitelli, PhD