Next Article in Journal
Reasoning on Figurative Language: A Preliminary Study on Children with Autism Spectrum Disorder and Klinefelter Syndrome
Previous Article in Journal
Paternal Preconception Every-Other-Day Ethanol Drinking Alters Behavior and Ethanol Consumption in Offspring
Open AccessArticle

Empagliflozin Ameliorates Type 2 Diabetes-Induced Ultrastructural Remodeling of the Neurovascular Unit and Neuroglia in the Female db/db Mouse

1
Diabetes and Cardiovascular Center, School of Medicine, University of Missouri, Columbia, MO 65212, USA
2
Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, MO 65212, USA
3
Electron Microscopy Core Facility, University of Missouri, Columbia, MO 65212, USA
4
Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO 65201, USA
5
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA
*
Author to whom correspondence should be addressed.
Brain Sci. 2019, 9(3), 57; https://doi.org/10.3390/brainsci9030057
Received: 16 January 2019 / Revised: 4 March 2019 / Accepted: 5 March 2019 / Published: 7 March 2019
(This article belongs to the Section Neuroglia)
Type 2 diabetes is associated with diabetic cognopathy. Anti-hyperglycemic sodium glucose transporter 2 (SGLT2) inhibitors have shown promise in reducing cognitive impairment in mice with type 2 diabetes mellitus. We recently described marked ultrastructural (US) remodeling of the neurovascular unit (NVU) in type 2 diabetic db/db female mice. Herein, we tested whether the SGLT-2 inhibitor, empagliflozin (EMPA), protects the NVU from abnormal remodeling in cortical gray and subcortical white matter. Ten-week-old female wild-type and db/db mice were divided into lean controls (CKC, n = 3), untreated db/db (DBC, n = 3), and EMPA-treated db/db (DBE, n = 3). Empagliflozin was added to mouse chow to deliver 10 mg kg−1 day−1 and fed for ten weeks, initiated at 10 weeks of age. Brains from 20-week-old mice were immediately immersion fixed for transmission electron microscopic study. Compared to CKC, DBC exhibited US abnormalities characterized by mural endothelial cell tight and adherens junction attenuation and/or loss, pericyte attenuation and/or loss, basement membrane thickening, glia astrocyte activation with detachment and retraction from mural cells, microglia cell activation with aberrant mitochondria, and oligodendrocyte–myelin splitting, disarray, and axonal collapse. We conclude that these abnormalities in the NVU were prevented in DBE. Empagliflozin may provide neuroprotection in the diabetic brain. View Full-Text
Keywords: astrocyte; endothelial cell; microglia; mitochondria; myelin; neuroglia; oligodendrocyte; pericyte; sodium glucose co-transporter 2 inhibitor (SGLT2i); white matter astrocyte; endothelial cell; microglia; mitochondria; myelin; neuroglia; oligodendrocyte; pericyte; sodium glucose co-transporter 2 inhibitor (SGLT2i); white matter
Show Figures

Figure 1

MDPI and ACS Style

Hayden, M.R.; Grant, D.G.; Aroor, A.R.; DeMarco, V.G. Empagliflozin Ameliorates Type 2 Diabetes-Induced Ultrastructural Remodeling of the Neurovascular Unit and Neuroglia in the Female db/db Mouse. Brain Sci. 2019, 9, 57.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop