Our Sleep, Brain Aging, and Waste Clearance
“Sleep is a non-negotiable biological state required for the maintenance of human life.…our need for sleep parallels those for air, food, and water.”— Grandner and Fernandez
In 2012, Maiken Nedergaard and her colleagues at the University of Rochester discovered the brain glymphatic pathway, the brain’s plumbing system similar to lymphatics in the body (but without lymph nodes), which consists of a network of fluid-filled and water channels (specifically aquaporin-4, AQP4, expressed on astrocytes) alongside (para) blood vessels to drain chemical waste, and facilitate movement of cerebrospinal fluid.
In early 2024, 2 Nature publications demonstrated that synchronized neurons can activate glymphatic waste clearance. Blocking neuronal firing prevented waste clearance (Figure below). The best summary for their work, positioning neurons as the master organizers for brain clearance, as articulated by the authors, is: “ neurons that fire together, shower together.” Gamma stimulation was shown to increase the arterial vasomotion (rhythmic oscillation/movement) and release of neuronal peptide molecules.
The 2 schematics below provide an updated version of our understanding of how glymphatics work. At left, below, you can see key components (neurons, AQP4, neuropeptide, the perivascular space, also known as Virchow-Robin space) with waste material accumulating around the artery (at top), which is subject to vasomotion, and the clearance of the waste material alongside the veins to lymphatics outside the brain (→ meningeal lymphatic vessels and neck lymph nodes). At right, you see the same flow pattern from around arteries to veins to the dural sinus of cerebrospinal fluid. The importance of brain macrophages (parenchymal border macrophages, PBM) is highlighted.
