Astrocyte Separation In Diabetic Mice: Six Degrees Of Separation: History Edit

Astrocytes (AC) are specialized connecting cells in the brain and structurally connect the neurovascular unit (NVU) mural cells to neurons.  ACs provide connection; communication for functional hyperemia in regions of increased neuronal activity.  Connections of AC end-feet allow for increased oxygen and nutrient substrate delivery to maintain an appropriately matched cerebral blood flow (CBF).  We previously published a paper in the Neuroglia section of Brain Science, which demonstrated observational ultrastructural detachment, separation and retraction of AC end-feet in the diabetic db/db female (DBC).  It was hypothesized that this loss of tightly adherent ACs could result in the known impaired cognition in DBC.  Additionally, it was hypothesized that glucose lowering by empagliflozin treatment could protect DBC remodeling.  Interestingly, we observed the mean number of 6.4 ACs/NVU in control heterozygous (CKC) vs, 1.88 ACs/NVU in DBC (p <0.05) and 5.86 ACs/NVU in empagliflozin DBE (p < 0.05) vs, DBC by hand counting capillary NVUs as follows: 22 in the CKC, 25 in DBC and 22 in DBE.  These findings indicate that empagliflozin provides neuroprotection via prevention of AC separation in DBE along with the protection of mural cells and remaining neuroglia in obese, insulin resistant, type 2 diabetic db/db DBC.