What is it about?
One of the most complex proteins discovered, subcommissural organ-spondin (SCO-spondin), is directly secreted by the SCO cells. It has also been proposed that SCO-spondin may remain soluble inside the CSF; however, its function in the adult brain is completely unknown. According to the results, we report the functional role for SCO-spondin in the adult brain. By expressing glucose transporter 2 (GLUT2), SCO cells can detect increases in CSF glucose levels in the context of hyperglycemia and release soluble SCO-spondin into the CSF. SCO-spondin interacts with the apex of cilia in dorsal ependymal cells (third ventricle) to temporarily slow CSF flow. Because CSF flow is important for regulating the concentration of glucose in the hypothalamic third ventricle, a temporarily decrease in CSF flow in hyperglycemia has a powerful effect on the glucose-sensing mechanism.
Featured Image
Photo by Elena Leya on Unsplash
Why is it important?
By integrating information from the literature and the results presented in this manuscript, we propose that in the brain, glucose sensing involves the coordination of three circumventricular organs: the SCO, choroid plexus, and hypothalamic ME. These structures enhance glucose entry into the cerebral ventricular system during hyperglycemia and coordinate the flow of CSF within the third ventricle to efficiently activate glucose-sensing neurons (in the hypothalamus).
Perspectives
From Liu and Fame, PlosBiology, Primer, 2013, “Ependymal cells SCOre sweet cerebrospinal fluid”. What are the potential outcomes of ependymal flow slowdown? Slower flow could extend the duration of glucose detection, since it would prolong the exposure time window for glucose-sensing organs to sample CSF glucose. However, decreased ependymal flow is also strongly associated with hydrocephalus, a neurological disorder characterized by excessive buildup of CSF in brain ventricles. Indeed, CSF composition and flow (i.e., speed and directionality) contribute to volume homeostasis. Nualart and colleagues provide compelling evidence demonstrating reduced ependymal flow and altered local CSF composition caused by hyperglycemia-induced SCO-spondin secretion. Notably, these observations are all made in the third ventricle, which connects the lateral ventricles to the fourth ventricle through the only two existing physiological narrowings of the brain ventricular system: the foramen of Monro and the aqueduct. Slowdown of flow through these narrowest portions of the ventricular system could disproportionately disrupt bulk CSF movement. When the authors analyze adult human brain, in which the SCO has diminished from its existence earlier in development, they discover that critical SCO elements are present in third ventricle ependyma, including SCO-spondin. This finding suggests that roles specific to the SCO in other species, including CSF-glucose sensing, may still be relevant in humans if carried out by this subpopulation of ependymal cells. Since hyperglycemia is a leading symptom of diabetes, these data in humans could further inform a mechanism for the clear, reproducible observation that diabetes drives idiopathic normal pressure hydrocephalus. According to the United States Centers for Disease Control and Prevention, 37.3 million Americans are living with diabetes, and 96.0 million American adults have prediabetes, an intermediate hyperglycemic borderline condition highly likely to progress to diabetes within 5 years. These findings sound the alarm: uncontrolled glucose levels could eventually impair CSF homeostasis.
Dr. Francisco Nualart
Universidad de Concepcion
Read the Original
This page is a summary of: Hyperglycemia increases SCO-spondin and Wnt5a secretion into the cerebrospinal fluid to regulate ependymal cell beating and glucose sensing, PLoS Biology, September 2023, PLOS,
DOI: 10.1371/journal.pbio.3002308.
You can read the full text:
Contributors
The following have contributed to this page
