Leptin receptor deficiency induces early, transient and hyperglycaemia-independent blood-brain barrier dysfunction

Scientific Reports
Noa CoremAyal Ben-Zvi

Abstract

Diabetes mellitus (DM) significantly increases susceptibility to central nervous system (CNS) pathologies, including stroke, vascular dementia, cognitive deficits and Alzheimer's disease. Previous studies (mostly using the streptozotocin model) suggested that blood-brain barrier (BBB) disruption is involved in these conditions. Here, we examined the integrity of brain capillaries and BBB permeability in Leprdb/db obesity-related diabetic mice. Surprisingly, significant BBB leakage was observed only in young mice at the pre-hyperglycemic stage. Thorough examination of barrier permeability at later diabetic stages showed no evidence for significant BBB leakage during the hyperglycemic state. Electron microscopy imaging of mice with short-term hyperglycaemia supported normal BBB permeability but indicated other stress-related changes in capillary ultrastructure, such as mitochondrial degeneration. Based on our study with this mouse genetic model of obesity-related DM, we suggest that previously reported hyperglycaemia-induced BBB leakage is most likely not the underlying mechanism of DM-related CNS pathologies. Finally we propose that BBB hyper-permeability might be an early and transient phenomenon while stress-related endothelia...Continue Reading

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Citations

Sep 3, 2019·Journal of Alzheimer's Disease : JAD·Patrick J SmithJames A Blumenthal
Apr 6, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yaan LiuWenting Zhang
Mar 17, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Sarah-Jane Leigh, Margaret J Morris
Jun 26, 2021·Pharmacology & Therapeutics·Sorabh Sharma, Craig E Brown

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Methods Mentioned

BETA
electron microscopy
confocal microscopy
PCR

Software Mentioned

C1
Nis
EZ
Zen10
ARRIVE
Angiotool
ImageJ
Elements

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