Chronic type 2 diabetes reduces the integrity of the blood-brain barrier by reducing tight junction proteins in the hippocampus

• Published in: Journal of Veterinary Medical Science Vol. 78; no. 6; pp. 957 - 962
• Main Authors: YOO, Dae Young, YIM, Hee Sun, JUNG, Hyo Young, NAM, Sung Min, KIM, Jong Whi, CHOI, Jung Hoon, SEONG, Je Kyung, YOON, Yeo Sung, KIM, Dae Won, HWANG, In Koo
• Format: Journal Article
• Language: English
• Published: Japan JAPANESE SOCIETY OF VETERINARY SCIENCE 2016; Japan Science and Technology Agency; The Japanese Society of Veterinary Science
• Subjects: Anatomy; Animals; Blood Glucose - analysis; blood-brain barrier; Blood-Brain Barrier - physiopathology; Blotting, Western; Claudin-5 - analysis; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - physiopathology; Female; Glycated Hemoglobin - analysis; hippocampus; Hippocampus - chemistry; Hippocampus - physiopathology; Male; Occludin - analysis; Rats; Rats, Zucker; tight junction; Tight Junction Proteins - physiology; type 2 diabetes; Zonula Occludens-1 Protein - analysis
• ISSN: 0916-7250; 1347-7439
• DOI: 10.1292/jvms.15-0589

In the present study, we investigated the effects of type 2 diabetes-induced hyperglycemia on the integrity of the blood–brain barrier and tight junction markers in the rat hippocampus. Forty-week-old diabetic (Zucker diabetic fatty, ZDF) rats and littermate control (Zucker lean control, ZLC) rats were used in this study. We evaluated the integrity of the blood–brain barrier by measuring sodium fluorescein extravasation and blood vessel ultrastructure. In addition, tight junction markers, such as zona occludens-1, occludin and claudin-5, were quantified by western blot analysis. ZDF rats showed significantly increased sodium fluorescein leakage in the hippocampus. Tight junction markers, such as occludin and claudin-5, were significantly decreased in the hippocampi of ZDF rats compared to those of ZLC rats. In addition, ZDF rats showed ultrastructural changes with phagocytic findings in the blood vessels. These results suggest that chronic untreated diabetes impairs the permeability of the hippocampal blood–brain barrier by down-regulating occludin and claudin-5, indicating that chronic untreated diabetes may cause hippocampus-dependent dysfunction.