title: Dynamic changes of Apo A1 mediated by LXR/RXR/ABCA1 pathway in brains of the aging rats with cerebral hypoperfusion.
abstract: Cerebral hypoperfusion or aging often results into the disturbances of cholesterol and lipoprotein, which have been tightly associated with numerous neurological and psychiatric diseases, such as vascular dementia. The pathway of liver X receptor-β (LXR-β)/retinoic X receptor-α (RXR-α)/ABCA1 plays a vital role in lipoprotein metabolism. However, there were no reports about the relationship between the signal molecules of the pathway and lipoprotein homeostasis in cerebral hypoperfusion models. Therefore, we aimed to detect the expression of the pathway molecules in the aging rat models of chronic cerebral hypoperfusion and to explore its underlying mechanism. The model with cerebral hypoperfusion was established by ligating of the bilateral common carotid arteries (2VO). The temporal blood flow in the model rats was significantly decreased 14 d, 21 d and 28 d after 2VO compared with the control. The serum levels of high-density lipoprotein (HDL) and total cholesterol (TC) were reached a peak at 14 d, then, they were gradually decreased. The changes of LXR-β, RXR-α, ABCA1 and apolipoprotein A1 (apo A1) of the pathway were consistent with the changes of HDL and TC. We conclude that LXR-β/RXR-α/ABCA1 and downstream genes apo A1 undergo dynamic changes during the process of cerebral hypoperfusion. The LXR-β/RXR-α/ABCA1 mediated apo A1 cholesterol may play a protective effect, and the effect only exists in a certain period of time.
authors.affiliation: Department of Pathology, Institute of Neuroscience, Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Linhui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lü
authors.affiliation: Department of Pathology, Institute of Neuroscience, Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Tian
authors.affiliation: Department of Pathology, Institute of Neuroscience, Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. Electronic address: liyu100@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D015140:Dementia, Vascular / Q000378:metabolism*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D047488:Retinoid X Receptors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047488:Retinoid X Receptors; C577834:Abca1 protein, rat
keywords: 2 vessel occlusion; 2VO; ABCA1; AD; ATP-binding cassette transporter A1; Alzheimer's disease; Apolipoprotein A1; BBB; HDL; LXR; Liver X receptor-β; RXR; Retinoic X receptor-α; VD; Vascular dementia; blood–brain barrier; high-density lipoprotein; liver X receptor; retinoid X receptor; vascular dementia