title: Chronic type 2 diabetes reduces the integrity of the blood-brain barrier by reducing tight junction proteins in the hippocampus.
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.
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, South Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Yoo
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Yim
authors.forename: Hyo Young
authors.initials: HY
authors.lastname: Jung
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Nam
authors.forename: Jong Whi
authors.initials: JW
authors.lastname: Kim
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Je Kyung
authors.initials: JK
authors.lastname: Seong
authors.forename: Yeo Sung
authors.initials: YS
authors.lastname: Yoon
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D015153:Blotting, Western; D062507:Claudin-5 / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006624:Hippocampus / Q000737:chemistry / Q000503:physiopathology*; D008297:Male; D062793:Occludin / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker; D062725:Tight Junction Proteins / Q000502:physiology*; D062826:Zonula Occludens-1 Protein / Q000032:analysis
chemical_list: D001786:Blood Glucose; D062507:Claudin-5; D006442:Glycated Hemoglobin; D062793:Occludin; D062725:Tight Junction Proteins; D062826:Zonula Occludens-1 Protein; C491510:Cldn5 protein, rat; C568987:Ocln protein, rat; C569044:Tjp1 protein, rat