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Hypothesis: Astrocyte Foot Processes Detachment from the Neurovascular Unit in Female Diabetic Mice May Impair Modulation of Information Processing—Six Degrees of Separation

1
Diabetes and Cardiovascular Center, University of Missouri School of Medicine, Columbia, MO 65212, USA
2
Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, MO 65212, USA
Brain Sci. 2019, 9(4), 83; https://doi.org/10.3390/brainsci9040083
Received: 14 March 2019 / Revised: 8 April 2019 / Accepted: 10 April 2019 / Published: 14 April 2019
(This article belongs to the Section Neuroglia)
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PDF [4166 KB, uploaded 14 April 2019]
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Abstract

Astrocytes via their foot processes (ACfp) are specialized connecting cells, and they structurally connect the neurovascular unit (NVU) mural cells to neurons. Astrocytes provide homeostatic mechanisms for structural connections and provide communication between the NVU and regional neurons for functional hyperemia in regions of increased neuronal activity (neurovascular coupling). Previously, our group has demonstrated a detachment, separation, and retraction of ACfp in diabetic db/db females (DBC). It was hypothesized that a loss of adherent ACfp/NVU could result in the known impaired cognition in DBC. Additionally hypothesized was that empagliflozin treatment could protect DBC ACfp/NVU remodeling. This study demonstrates a significant loss of ACfp/NVU numbers in DBC and a protection of this loss by empagliflozin treatment (DBE). The number of intact ACfp/NVU was 6.45 ± 1.1 in control heterozygous (CKC) vs. 1.88 ± 0.72 in DBC (p < 0.05) and 5.86 ± 0.88 in DBE vs. DBC (p < 0.05) by visually hand-counting the capillary NVUs (22 in CKC, 25 in DBC, and 22 in DBE). These findings suggest that empagliflozin provides neuroprotection via the prevention of ACfp separation in DBE as compared to diabetic DBC. Furthermore, a loss of ACfp/NVU numbers in DBC may correspond with a negative modulation of informational processing, and the protection of ACfp/NVU numbers could provide a protective modulation in DBE models. View Full-Text
Keywords: astrocyte; basement membrane; astrocyte foot processes; endothelial cells; pericyte’s; neurovascular unit; neurovascular coupling; neuron astrocyte; basement membrane; astrocyte foot processes; endothelial cells; pericyte’s; neurovascular unit; neurovascular coupling; neuron
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Hayden, M.R. Hypothesis: Astrocyte Foot Processes Detachment from the Neurovascular Unit in Female Diabetic Mice May Impair Modulation of Information Processing—Six Degrees of Separation. Brain Sci. 2019, 9, 83.

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