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- Title
Changes of Blood-Brain Barrier and Brain Parenchymal Protein Expression Levels of Mice under Different Insulin-Resistance Conditions Induced by High-Fat Diet.
- Authors
Ogata, Seiryo; Ito, Shingo; Masuda, Takeshi; Ohtsuki, Sumio
- Abstract
Purpose: The purpose of the present study was to investigate changes of blood-brain barrier (BBB) and brain parenchymal protein expression due to type II diabetes mellitus (T2DM) induced by a high-fat diet (HFD) by using SWATH-based quantitative proteomics. Methods: Mice were fed a HFD for 2 or 10 weeks, and then SWATH-based quantitative proteomic analysis, western blot analysis, immunohistochemistry and functional transport studies were performed. Results: In brain capillaries, expression levels of BBB transporters (Glut1, P-glycoprotein) and tight-junction proteins (claudin-5, occludin) were significantly reduced in HFD mice at 2 weeks, but recovered to the levels in the normal diet (ND) group at 10 weeks. P-glycoprotein function at the BBB was reduced at 2 weeks. In the cerebral cortex and hippocampus, neurofilament, which is important for neuronal function, was decreased in HFD mice at 2 weeks, but recovered at 10 weeks. Conclusion: Our results suggest that changes in the status of insulin resistance influence expression of BBB transporters, which in turn may alter the expression of cognitive function-related proteins.
- Subjects
OCCLUDINS; BLOOD-brain barrier; HIGH-fat diet; PROTEIN expression; BRAIN proteins; TYPE 2 diabetes; CEREBRAL cortex
- Publication
Pharmaceutical Research, 2019, Vol 36, Issue 10, pN.PAG
- ISSN
0724-8741
- Publication type
Article
- DOI
10.1007/s11095-019-2674-8