The Brain Never Rests

Written by Kimiya Mansour | Edited by Josephine Chan

Photo by Tara Winstead

What happens to your brain when you sleep? According to the Nedergaard Laboratory at the University of Rochester Medical Center, as norepinephrine levels in the body decrease, promoting sleep, a new system in the brain is activated: the glymphatic system [1]. The word “glymphatic” might sound similar to the lymphatic system, another body system that you may be familiar with. This system plays a role in immunity within the body and helps clear away unwanted byproducts of our organs by transferring them to the liver for secretion [2]. In the brain, however, the Nedergaard lab discovered that the glymphatic system actually replaces the lymphatic system [3] [4]. The term “glymphatic” is an attribute to glial cells, non-neuronal cells that cover 98.4% of all brain blood vessels and assist with the everyday functions of the brain [4]. To visualize how the glymphatic system aids in byproduct secretion, the Nedergaard lab utilized fluorescent tracers to track the movement of proteins. When these tracers were injected into the brains of live mice, it was found that the tracers mixed with cerebrospinal fluid (CSF), which is a clear, watery, fluid within the brain [5]. Afterward, the CSF and tracers entered the channels around the arteries in the brain before exiting the brain via another channel [5] [6]. This intricate methodology of eliminating toxic protein accumulation proves that the human brain is capable of more functions than scientists have thought of before, which formulates the notion that the field of neurobiology still has a lot of mysteries waiting to be solved.

Perhaps one of the unlocked mysteries of the glymphatic system is that it only activates during sleep. [7]. As such, the important task of removing protein accumulation is typically done during sleep [7]. However, if an individual is sleep-deprived, this cannot be done as effectively, potentially leading to serious health complications. For example, a sleep-deprived brain has been found to contain higher levels of amyloid-beta protein (AB), which is thought to play a significant role in Alzheimer’s disease (AD) [8]. AD drastically lowers one’s quality of life and is characterized by the inability to recall and retain information due to the accumulation of AB [10]. More specifically, in an AD patient’s brain, the build-up of AB enlarges the para-arterial space in the brain, reducing glymphatic flow and byproduct elimination [9]. Therefore, lead researchers hope to gain an in-depth understanding of this system and how it can influence the development of therapeutic measures for AD, as well as mental illnesses [9]. 

It is important to note that, although several research projects have been developed based on the accumulation of the protein and its influence on the glymphatic system, a holistic approach is required when researching neurodegenerative diseases [11]. Research on the glymphatic system is still in its infancy and future projects need to be conducted to offer viable therapeutic methods in humans, such as why wakefulness prevents the function of the glymphatic system. 

References:

1. Plog, B. A, Nedergaard, M. (2018). “The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future.” Annual review of pathology, 13:379-394.
2. “Lymphatic system.” Better Health, 19 July 2017, https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/lymphatic-system. Accessed 27 July 2022.
3. Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., Benveniste, H., Vates, G. E., Deane, R., Goldman, S. A., Nagelhus, E. A., & Nedergaard, M. (2012). A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Science translational medicine, 4:147ra111.
4. Nedergaard, Maiken. “Glymphatic system.” University of Rochester Medical Center, https://www.urmc.rochester.edu/labs/nedergaard/projects/glymphatic-system.aspx. Accessed 15 July 2022.
5. Nedergaard, M. (2014). “Neuroscience. Garbage truck of the brain.” Science, 340: 1529-30.
6. Ray, L., Iliff, J.J., Heys, J.J. (2019) Analysis of convective and diffusive transport in the brain interstitium. Fluids Barriers CNS, 16:6
7. Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., O’Donnell, J., Christensen, D. J., Nicholson, C., Iliff, J. J., Takano, T., Deane, R., & Nedergaard, M. (2013). Sleep drives metabolite clearance from the adult brain. Science, 342: 373–377
8. Shokri-Kojori, E., Wang,  G., Wiers, C. E., Volkow, N. D. (2018) “Β-Amyloid Accumulation in the Human Brain after One Night of Sleep Deprivation.” Proceedings of the National Academy of Sciences, 115: 4483–4488
9. Jessen, N. A., Munk, A. S., Lundgaard, I., & Nedergaard, M. (2015). The Glymphatic System: A Beginner’s Guide. Neurochemical research, 40: 2583–2599.
10. “Alzheimer’s Disease Fact Sheet.” National Institute on Aging, 8 July 2021, https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet#:~:text=Alzheimer%27s%20disease%20is%20a%20brain,first%20appear%20later%20in%20life. Accessed 29 July 2022.
11. Hauglund, N., L. Pavan, C., Nedergaard, M. (2020) “Cleaning the Sleeping Brain – the Potential Restorative Function of the Glymphatic System.” Current Opinion in Physiology, 15: 1–6.