Amelioration of Cholesterol Rich diet-induced Impaired Cognition in AD Transgenic Mice by an LXR Agonist TO901317 Is Associated with the Activation of the LXR-β-RXR-α-ABCA1 Transmembrane Transport System and Improving the Composition of Lipid Raft

• Published in: Experimental aging research 2023-05, Vol.49 (3), p.214-225
• Main Authors: Na, Yang, Ke, Lin, Jie, Zhang, Jinping, Wang, Tao, Meng, Jie, Zhu, Liu, Yang, Yueqin, Zhou
• Format: Article
• Language: English
• Subjects: ABCA1 protein; Aging; Agonists; Amyloid Precursor Protein Secretases - metabolism; Animals; Aspartic Acid Endopeptidases - metabolism; ATP Binding Cassette Transporter 1; ATP-binding protein; Caveolin; Caveolin 1 - metabolism; Caveolin-1; Cholesterol; Cognition; Cognitive ability; Colorimetry; Diet; Enzyme-linked immunosorbent assay; Exploration; High density lipoprotein; Humans; Liver X Receptors - metabolism; Low density lipoprotein; Male; Membrane Microdomains - metabolism; Memory; Mice; Mice, Transgenic; Orphan Nuclear Receptors - metabolism; Protein Transport; Proteins; Retinoid X Receptor alpha - metabolism; Retinoid X receptors; Spatial discrimination learning; Spatial memory; Transgenic animals; Transgenic mice; Western blotting; β-Site APP-cleaving enzyme 1
• ISSN: 0361-073X; 1096-4657
• DOI: 10.1080/0361073X.2022.2095605

It has been reported that LXR agonist can inhibit Aβ generation and alleviate Aβ-induced various adverse reactions in vivo and in vitro experiments, but the mechanisms have not been clarified. The study aimed to observe the effect of LXR agonist TO901317 on the cognitive function of AD transgenic mice fed with cholesterol-rich diet (CRD), and to explore the possible mechanism. Methods: 32 male 6-month-old double transgenic AD mice were enrolled and randomly divided into 4 groups: control (normal diet) group, CRD treatment group, TO901317 treatment group and GSK2033 treatment group. After 3 month, Morris water maze was for the changes of spatial exploration and memory ability; ELISA was for detecting the production of Aβ42 in the brain; the concentration of total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) in serum were detected by cholesterol enzyme colorimetry; Finally, the expression of LXR-β, RXR-α, ABCA1, caveolin-1, BACE1 and APP at protein level in the brains was measured by Western blotting. Compared with the control group, the learning, memory ability and spatial exploration ability of the mice were more significantly serious in the CRD group (P