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

Dae Young YOO; Hee Sun YIM; Hyo Young JUNG; Sung Min NAM; Jong Whi KIM; Jung Hoon CHOI; Je Kyung SEONG; Yeo Sung YOON; Dae Won KIM; In Koo HWANG

doi:10.1292/jvms.15-0589

Anatomy

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

Dae Young YOO, Hee Sun YIM, Hyo Young JUNG, Sung Min NAM, Jong Whi KIM, Jung Hoon CHOI, Je Kyung SEONG, Yeo Sung YOON, Dae Won KIM, In Koo HWANG

Author information

Dae Young YOO
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, South Korea
Hee Sun YIM
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangneung-Wonju National University, Gangneung 25457; South Korea
Hyo Young JUNG
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, South Korea
Sung Min NAM
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, South Korea
Jong Whi KIM
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, South Korea
Jung Hoon CHOI
Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, South Korea
Je Kyung SEONG
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, South Korea
KMPC (Korea Mouse Phenotyping Center), Seoul National University, Seoul 08826, South Korea
Yeo Sung YOON
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, South Korea
KMPC (Korea Mouse Phenotyping Center), Seoul National University, Seoul 08826, South Korea
Dae Won KIM
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangneung-Wonju National University, Gangneung 25457; South Korea
In Koo HWANG
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, South Korea
KMPC (Korea Mouse Phenotyping Center), Seoul National University, Seoul 08826, South Korea

Keywords: blood-brain barrier, hippocampus, tight junction, type 2 diabetes

JOURNAL FREE ACCESS

2016 Volume 78 Issue 6 Pages 957-962

DOI https://doi.org/10.1292/jvms.15-0589

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Abstract

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.

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