Many of us are relatively familiar with the lymphatic system; performs a number of functions, such as removing metabolic waste from the gaps between cells , called the interstitial space. However, the central nervous system, which comprises the brain and spinal cord, does not have any actual lymphatic vessels, and because the central nervous system is highly active, metabolic wastes can accumulate rapidly. But the body needs to eliminate cellular waste in some way, and that’s where the glyphatic system comes in : the one in charge of removing waste from the brain.
Before the discovery of this brain-based garbage disposal system, scientists believed that each individual cell was responsible for its own metabolic debris such as beta-amyloid, the protein associated with Alzheimer’s disease.
Astroglía
The term “glyphatic” was coined by Maiken Nedergaard, a Danish neuroscientist who discovered such a system. The name is a reference to glial cells, which are vital to this waste disposal system.
Glial cells obtain relatively little coverage, compared to neurons, despite being so numerous in the brain. For a long time they were considered little more than support cells, but now they are held in higher regard. Glia protect, nourish and isolate neurons. They also play a key role in the immune system and, as we now know, in the glyphatic system as well.
In particular, a type of glial cell known as an astroglia is important in this regard. Receptors, called aquaporin-4 channels, in these cells allow cerebrospinal fluid to move into the central nervous system, creating a current that diverts the fluid. Remember that cerebrospinal fluid is a transparent substance that surrounds the central nervous system and provides mechanical and immunological protection, among other things.
The glyphatic system, which runs parallel to the arteries, also harnesses the pulse of the blood in the circulation to help keep everything moving. As the blood vessels rhythmically expand, they drive the exchange of compounds between the interstitial space and the cerebrospinal fluid.
The glyphatic system connects with the lymphatic system of the rest of the body in what is known as the dura , a thick membrane of connective tissue that covers the central nervous system.
The importance of sleep
Following the discovery by neuroscientist Nedergaard, a series of experiments were carried out in mice to develop a better understanding of how this system worked and when it was most active. In particular, the team focused on sleep and Alzheimer’s disease.
Nedergaard and his team found that the glyphatic system was busier while the animals slept : the volume of the interstitial space increased by 60% while the mice slept. This increased volume also boosted the exchange of cerebrospinal fluid and interstitial fluid, accelerating amyloid clearance. They concluded that: “The restorative function of sleep may be a consequence of the enhanced clearance of potentially neurotoxic waste products that accumulate in wakefulness.”
This initial work inspired a wave of new studies, such as the one published in 2019 in the magazineJournal of Neurosciencein which the researchers looked at the impact of high blood pressure on the function of the glyphatic system.
Over time, high blood pressure causes blood vessels to lose their elasticity and become increasingly rigid. Because the regular pulsation of the arterial walls drives the glyphatic system, this rigidity impedes its function.
Using a mouse model of hypertension, the scientists demonstrated that the stiffness of the artery induced by high blood pressure interfered with the way the garbage disposal system worked; It prevented it from efficiently getting rid of large molecules in the brain, such as beta-amyloid. This finding could help explain why scientists have found links between high blood pressure and cognitive decline and dementia.
Parkinson’s
Parkinson’s disease is another condition characterized by the accumulation of proteins in the brain. In this case, the protein is alpha-synuclein. In this disease there is a disruption in the brain’s dopamine pathways. These pathways play an important role in sleep-wake cycles and circadian rhythms; therefore, Parkinson’s patients often experience sleep disturbances.
A review published in Neuroscience & Biobehavioral Reviews proposed that disrupted sleep patterns could hinder the glyphatic removal of wastes, including alpha-synuclein, that help build up in the brain.
Diabetes
Beyond a possible role in neurological conditions, some scientists have investigated how alterations in the glyphatic system may be involved in the cognitive symptoms of diabetes. They have shown that diabetes can affect a variety of cognitive functions, both early in the disease and in the future.
Some researchers wonder if the glyphatic system could also be involved in this process. A study in mice used magnetic resonance imaging to visualize the movement of cerebrospinal fluid in the hippocampus, a part of the brain involved in the formation of new memories, among other tasks. The scientists found that in mice with type 2 diabetes, cerebrospinal fluid clearance was “reduced by a factor of three.” They also found a correlation between cognitive deficits and the deterioration of the glyphatic system: if the garbage was not cleaned, the difficulties in thinking skills began.
Aging
As we age, a certain level of cognitive decline is almost inevitable. There are a wide range of factors involved, and some scientists believe that the glyphatic system could be key.
A study published in 2014 investigated the efficiency of the glyphatic systems of mice as they aged. The authors found a “dramatic decrease in efficiency.”
In a review of the glyphatic system and its role in disease and aging, the authors write that reduced activity in the system as we age could “contribute to the accumulation of hyperphosphorylated and misfolded proteins,” increasing the risk of neurodegenerative diseases and, perhaps, exacerbating cognitive dysfunction.
It is clear that we still know relatively little about the glyphatic system. However, because it cleanses our most sensitive and complex organ, it is likely to influence our overall health to some degree. It won’t contain all the answers to our questions about neurodegenerative diseases, but it could pave the way for exciting new perspectives for the future.
Referencia: Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson’s disease DOI: https://doi.org/10.1016/j.neubiorev.2019.05.016 / Impaired Glymphatic Transport in Spontaneously Hypertensive Rats. Journal of Neuroscience 17 June 2019, 1974-18; DOI: https://doi.org/10.1523/JNEUROSCI.1974-18.2019 / Impairment of the glymphatic system after diabetes . First Published July 21, 2016 Research Article. DOI: https://doi.org/10.1177/0271678X16654702
