Poor Sleep and its Contribution to Development of Neurodegenerative Disease

Author: Evelyn Fistler

Editor: Elena Bobric

Introduction

Many people consider sleep to be a way to rest the body, where some aim for a good 7-8 hours every night. However, there are often times where some find themselves sleeping less than that, or even barely sleeping at all. Few may suffer from insomnia or are susceptible to disruptions during sleep which many think may cause a bad mood or exhaustion throughout the day, whether one has a project to finish or is working late.

Physical symptoms are often presentable when someone does not get enough sleep, but people may not consider the biological factors of sleep and how impactful it is on brain health and overall cognition function. Sleep is important, and without it, the brain and nervous system could be negatively affected, where complications such as neurodegeneration and even development of disease may occur.

Neuroinflammation—What is it?

Neuroinflammation causes both protective and detrimental effects in the brain, where even though it acts as a defense against infections, injuries and trauma, degeneration and neurological damage may occur. Activation of glial cells, which are cells that transport cerebrospinal fluid, causes the flow of ions and glucose, and the release of inflammatory molecules due to their response to beta-amyloid (Aβ) plaques. These play a role in neuroinflammation and are often associated with the progression of neurodegenerative diseases (Adamu, et al, 2024).

How does it happen?

Obesity, unhealthy eating habits, stress, and loss of sleep are often associated with neuroinflammation and development of neurodegenerative diseases. More specifically, increased levels of cytokines due to oxidative stress, and change in blood-brain barrier (BBB) permeability are consistent factors. Through various areas, activation of signaling pathways may include ones involved with inflammation, leading to the release of cytokines, which can in turn, stimulate further inflammation. Cytokines also help regulate sleep, but increased levels of pro-inflammatory cytokines may occur due to sleep deprivation, enabling neuroinflammation. They may also disrupt the BBB, cause increased permeability through disruption of tight junctions and allow unwanted cells in the brain. Furthermore, if changes in the BBB occur, barrier collapsation and neuroinflammation will ensue (Sun, et al, 2022).

During sleep and while the body is resting, waste removal and fluid redistribution is increasingly active. The brain has the ability to remove unwanted proteins to prevent buildup, and it is called the Glymphatic System.

Glymphatic System—What is it?

The glymphatic system is active once people fall asleep and acts as a waste system that aids in elimination of soluble proteins and metabolites such as Beta-Amyloid that reside within the central nervous system (CNS) while also distributing glucose, lipids, and neurotransmitters (Jessen, et al, 2015). Through the subarachnoid space, an area located within the brain and spinal cord, bulk movement of cerebrospinal fluid mixes with interstitial fluid, moving through perivascular spaces and eventually draining through the peripheral lymphatic system, where proteins and excess fluid will then leak out of blood capillaries and into tissues while being filtered and then redistributed through the bloodstream (Hablitz, et al, 2021).

Template Created in https://BioRender.com

Template Created in https://BioRender.com (Iliff, et al, 2012).

How does this contribute to neurodegenerative diseases?

Through a neuropathological perspective, Alzheimer’s Disease (AD) is commonly associated with deposition of amyloid plaque and neurofibrillary tau tangles that impact the brain, causing cognitive issues and deterioration over time. Seen through clinical manifestations, AD may include insomnia or sleep disruptions that are further associated with cognitive decline, which leaves researchers studying the glymphatic system, considering that it is a critical contribution to sleep. Because the glymphatic system helps regulate waste removal for plaque, disruption of its functions is suggested to contribute to buildup of plaque that attaches to neurons and causes cell death (Verghese, et al, 2022).

Conclusion—Poor Sleep and How It Affects the Brain

Studies suggest that poor sleep leaves the brain susceptible to impairment and dysfunction. Because the brain needs the glymphatic system to regulate toxins and prevent disease, sleep cycles allow for this to happen, while letting the body restore energy. The stages of sleep are important for the brain's health but can impact cognition if disrupted. Issues with memory recall are prevalent and elevated stress is a common factor of consistent sleep disruption and can even cause neuron malfunction and loss of connections. The brain can only do one major activity at a time, which is why the glymphatic system activates during sleep, when the body is unconscious and response to external stimuli is limited (Eugene & Masiak, 2015).

What Next?

Furthering studies on how people can optimize rest and sleep with minimal disruptions may help brain health and ensure functionality. Additionally, research on the Glymphatic system and waste removal suggests potentially therapeutic effects on individuals through lifestyle choices such as consistent physical exercise, sleeping on the right lateral position for efficient glymphatic transport, avoiding heavy alcohol consumption as it is associated with higher risk of developing AD through neuroinflammation, and minimizing stress as best as possible due to long-term stress being a major contribution to AD development (Reddy & Van Der Werf, 2020).

Understanding all biological ranges of cerebrospinal fluid flow and how physiological mechanisms aid in redistribution of this fluid throughout the body will help researchers better understand how to prevent disease development (Hablitz, et al, 2021).

References

Adamu, A., Li, S., Gao, F., & Xue, G. (2024). The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets. Frontiers in aging neuroscience, 16, 1347987. https://doi.org/10.3389/fnagi.2024.1347987

Eugene, A. R., & Masiak, J. (2015). The Neuroprotective Aspects of Sleep. MEDtube science, 3(1), 35–40.

Hablitz, L. M., & Nedergaard, M. (2021). The Glymphatic System: A Novel Component of Fundamental Neurobiology. The Journal of neuroscience : the official journal of the Society for Neuroscience, 41(37), 7698–7711. https://doi.org/10.1523/JNEUROSCI.0619-21.2021

Jessen, N. A., Munk, A. S., Lundgaard, I., & Nedergaard, M. (2015). The Glymphatic System: A Beginner's Guide. Neurochemical research, 40(12), 2583–2599. https://doi.org/10.1007/s11064-015-1581-6

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Sun, Y., Koyama, Y., & Shimada, S. (2022). Inflammation From Peripheral Organs to the Brain: How Does Systemic Inflammation Cause Neuroinflammation?. Frontiers in aging neuroscience, 14, 903455. https://doi.org/10.3389/fnagi.2022.903455

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