Probucol prevents blood-brain barrier dysfunction and cognitive decline in mice maintained on pro-diabetic diet

Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease
John MamoRyusuke Takechi

Abstract

An emerging body of evidence consistently suggests that compromised blood-brain barrier integrity may be causally associated with cognitive decline induced by type-2 diabetes. Our previous studies demonstrated that selected anti-inflammatory/anti-oxidative agents can preserve the integrity of blood-brain barrier and prevent neuroinflammation in mouse models of dysfunctional blood-brain barrier. Therefore, we have tested whether the previously proven blood-brain barrier protective agent, probucol, can prevent blood-brain barrier breakdown and cognitive decline in a dietary-induced murine model of diabetic insulin resistance. After 6-month chronic ingestion of a diet high in fat and fructose, the mice became insulin resistant. The high-fat and high-fructose-fed mice showed significant cognitive decline assessed by Morris water maze, concomitant with significant elevations in cortical and hippocampal glial acidic fibrillary protein and Fluoro Jade-C staining, indicating heightened neuroinflammation and neurodegeneration, respectively. The integrity of blood-brain barrier in high-fat and high-fructose-fed mice was substantially compromised, and this showed a significant association with heightened neurodegeneration. Co-provision of...Continue Reading

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Citations

Jan 4, 2020·GeroScience·Kiran ChaudhariShao-Hua Yang
Feb 23, 2020·Neurobiology of Disease·Cutler T LewandowskiMary Jo LaDu
Jun 29, 2021·Neuroscience and Biobehavioral Reviews·Mikayla A Payant, Melissa J Chee
Aug 10, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Kai KangDeshan Li

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Methods Mentioned

BETA
Flow Cytometry
enzyme-linked immunosorbent assay
confocal microscopy
FACS
ELISA

Software Mentioned

FlowJo
HOMA Calculator
FCAP Array
Volocity
HVS Image

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