Sensing sugar in brain; subcommissural organ function

“

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.

”