January 15, 2023
Author: Manish Verma
Editor: Dr. Jitendra Kumar Sinha
We are all aware of how difficult it may be to remember which parts of the brain are responsible for certain processes. According to one research, the human brain has more than 180 distinct brain regions. While certain areas have apparent roles, others may appear insignificant but play a critical role in brain activity. To that list, researchers have recently uncovered a previously unknown component of brain structure that serves as both a protective barrier and a platform for immune cells to detect for signals of inflammation and infection.
The human brain is reticent to disclose its secrets, which range from the intricacy of neural networks to fundamental biological processes and structures. Only lately have developments in molecular biology and neuroimaging made it possible for researchers to examine the live brain at a degree of depth that was previously unachievable, solving many of its mysteries.
The most recent finding, reported in the journal Science, involves a previously unidentified part of the structure of the brain that serves as a barrier of defense and a base from which immune cells keep an eye out for inflammation and infection in the brain.
Nedergaard and her colleagues have altered the understanding of the underlying mechanics of the human brain and made substantial contributions to the field of neuroscience, including outlining the many vital tasks of previously unnoticed cells in the brain termed glia and the brain’s unique waste clearance process, which the lab designated the glymphatic system. Due to this discovery, researchers claim that we now have a far better understanding of the complex role that cerebrospinal fluid (CSF) plays in maintaining the brain’s immunological defenses as well as in separating and regulating the flow of CSF in and around the brain.
Figure 1 –
A novel structural component of the brain dubbed SLYM, short for “Subarachnoidal LYmphatic-like Membrane“, which serves as a platform for immune cells to monitor the brain and a barrier.
[Credit: University of Copenhagen]
The study focuses on the membranes that surround the brain, separating it from the rest of the body and maintaining its CSF bath. The dura, arachnoid, and pia matter are the three separate layers that make up the meningeal layer, which is commonly acknowledged as a barrier. The newly identified layer, which the researchers call the SLYM, an acronym for Subarachnoidal LYmphatic-like Membrane, further splits the region underneath the arachnoid layer, the subarachnoid space, into two compartments. Even though SLYM is mostly studied in mice, the authors claim that it is also present in the adult human brain.
The SLYM is a mesothelium-type membrane, which also lines the lungs and heart in addition to other bodily organs. Normally, mesothelia encircle and protect organs while also hosting immune cells.
First author of the paper Mllgrd raised the possibility that a comparable membrane may exist in the central nervous system. His work focuses on the systems of barriers that safeguard the brain as well as developmental neurobiology. The new membrane is very thin and fragile, with just one or a few cells in thickness. However, the SLYM is a tight barrier that only allows extremely tiny molecules to get through; it appears to segregate “clean” from “dirty” CSF.
This last observation suggests that SLYM may have a function in the glymphatic system, which needs a regulated flow and exchange of CSF, enabling new CSF to enter while flushing toxic proteins linked with Alzheimer’s and other neurological illnesses from the central nervous system. The Center for Translational Neuromedicine at the University of Rochester recently received a $13 million grant from the National Institutes of Health’s BRAIN Initiative to further its study into the mechanics of the glymphatic system.
The SLYM also seems crucial to the brain’s protective mechanisms. Immune cells are naturally present in the central nervous system, and the integrity of the membrane limits the entry of extraneous immune cells. Interestingly, the SLYM appears to have its own population of central nervous system immune cells, which employ the SLYM for surface-brain monitoring, allowing them to scan flowing CSF for indications of infection.
Together, the findings suggest that alterations in SLYM function may cause or aggravate disorders such as multiple sclerosis, central nervous system infections, and Alzheimer’s. They also suggest that SLYM function may influence medication and gene therapy delivery to the brain, which will need to be considered when new generations of biologic medicines are developed.
Keywords:
SLYM – Subarachnoidal LYmphatic-like Membrane
CSF – Cerebrospinal Fluid
AD – Alzheimer’s Disease
MS – Multiple Sclerosis
References:
- Møllgård, K., Beinlich, F. R. M., Kusk, P., Miyakoshi, L. M., Delle, C., Plá, V., Hauglund, N. L., Esmail, T., Rasmussen, M. K., Gomolka, R. S., Mori, Y., & Nedergaard, M. (2023). A mesothelium divides the subarachnoid space into functional compartments. Science (New York, N.Y.), 379(6627), 84–88. https://doi.org/10.1126/science.adc8810
- Ghosh, S., Durgvanshi, S., Agarwal, S., Raghunath, M., & Sinha, J. K. (2020). Current Status of Drug Targets and Emerging Therapeutic Strategies in the Management of Alzheimer’s Disease. Current neuropharmacology, 18(9), 883–903. https://doi.org/10.2174/1570159X18666200429011823