LIPOXIN A(4) METHYL ESTER ALLEVIATES VASCULAR COGNITION IMPAIRMENT BY REGULATING THE EXPRESSION OF PROTEINS RELATED TO AUTOPHAGY AND ER STRESS IN THE RAT HIPPOCAMPUS

摘要

Since autophagy and endoplasmic reticulum stress mechanisms are involved in some neurodegenerative and cerebral vascular diseases, we suspected that similar mechanisms might participate in vascular cognitive impairments induced by chronic cerebral hypoperfusion. Lipoxin A(4) methyl ester (LXA(4) ME) is an inflammation inhibitor that exhibits potent protective effects in experimental stroke models. In an earlier study, we found that LXA(4) ME improved cognitive deficit in a rat model of vascular cognitive impairment created using bilateral common carotid artery ligation (BCCAL) and two-vessel occlusion (2VO). In this study, LXA(4) ME treatment of 2VO rats improved brain morphological defects. We found that LXA(4) ME reduced the expression of some autophagy-and ERS-related factors in the hippocampus of 2VO rats, namely C/EBP homologous protein, beclin1 and the ratio of microtubule-associated protein light chain 3 II (LC3-II) to LC3-I. By contrast, LXA(4) ME upregulated the protein expression of phospho-mTOR, total-mTOR, glucose-regulated protein 78 and spliced and unspliced X-box binding protein-1 mRNA. Differential protein regulation by LXA(4) ME might underlie its ability to protect cognition after chronic cerebral hypoperfusion.