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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

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Title: 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
Authors: Na, Yang, Ke, Lin, Jie, Zhang, Jinping, Wang, Tao, Meng, Jie, Zhu, Liu, Yang, Yueqin, Zhou
Source: Experimental Aging Research. May/Jun2023, Vol. 49 Issue 3, p214-225. 12p. 1 Diagram, 2 Charts, 4 Graphs.
Subjects: Alzheimer's disease prevention, Learning assessment, Brain metabolism, Protein metabolism, In vitro studies, Memory, Animal behavior, In vivo studies, Animal experimentation, Western immunoblotting, Cognition, Cell receptors, Low density lipoproteins, Amyloid beta-protein precursor, Membrane glycoproteins, DNA-binding proteins, Enzyme-linked immunosorbent assay, Research funding, Colorimetry, High density lipoproteins, Dietary fats, Space perception, Cholesterol, Carrier proteins
Abstract: 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<0.05); The contents of TC and LDL in the serum and the production of Aβ42 in the brains were significantly increased (P<0.05), but HDL was remarkably decreased (P<0.05); The protein levels of LXR-β, RXR-α and ABCA1 were also significantly decreased (P<0.05); The expression of caveolin-1, APP and BACE1 were evidently increased (P<0.05). However, after treatment with TO901317, the impaired learning and memory and spatial exploration ability of the mice were significantly improved (P<0.05); The contents of TC and LDL in serum and the production of Aβ42 in the brains were significantly decreased (P<0.05), but HLD was increased (P<0.05); The protein levels of LXR-β, RXR-α, ABCA1were all significantly increased (P<0.05), while, the expression of caveolin-1, APP and BACE1 were all significantly decreased (P<0.05). All the changes were reversed by GSK2033 (P<0.05). TO901317 attenuated the more serious impairment of spatial exploration, learning and memory in transgenic AD mice induced by CRD, and the mechanism may be that TO901317 could activate the LXR-β/RXR-α/ABCA1 transmembrane transport system, promote the cholesterol efflux, and decreased caveolin-1, APP and BACE1, further reduce Aβ42 in the brains. [ABSTRACT FROM AUTHOR]
Copyright of Experimental Aging Research is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: 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
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  Data: &lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Na%2C+Yang%22&quot;&gt;Na, Yang&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Ke%2C+Lin%22&quot;&gt;Ke, Lin&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Jie%2C+Zhang%22&quot;&gt;Jie, Zhang&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Jinping%2C+Wang%22&quot;&gt;Jinping, Wang&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Tao%2C+Meng%22&quot;&gt;Tao, Meng&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Jie%2C+Zhu%22&quot;&gt;Jie, Zhu&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Liu%2C+Yang%22&quot;&gt;Liu, Yang&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Yueqin%2C+Zhou%22&quot;&gt;Yueqin, Zhou&lt;/searchLink&gt;
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22Experimental+Aging+Research%22&quot;&gt;Experimental Aging Research&lt;/searchLink&gt;. May/Jun2023, Vol. 49 Issue 3, p214-225. 12p. 1 Diagram, 2 Charts, 4 Graphs.
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  Data: 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&lt;0.05); The contents of TC and LDL in the serum and the production of Aβ42 in the brains were significantly increased (P&lt;0.05), but HDL was remarkably decreased (P&lt;0.05); The protein levels of LXR-β, RXR-α and ABCA1 were also significantly decreased (P&lt;0.05); The expression of caveolin-1, APP and BACE1 were evidently increased (P&lt;0.05). However, after treatment with TO901317, the impaired learning and memory and spatial exploration ability of the mice were significantly improved (P&lt;0.05); The contents of TC and LDL in serum and the production of Aβ42 in the brains were significantly decreased (P&lt;0.05), but HLD was increased (P&lt;0.05); The protein levels of LXR-β, RXR-α, ABCA1were all significantly increased (P&lt;0.05), while, the expression of caveolin-1, APP and BACE1 were all significantly decreased (P&lt;0.05). All the changes were reversed by GSK2033 (P&lt;0.05). TO901317 attenuated the more serious impairment of spatial exploration, learning and memory in transgenic AD mice induced by CRD, and the mechanism may be that TO901317 could activate the LXR-β/RXR-α/ABCA1 transmembrane transport system, promote the cholesterol efflux, and decreased caveolin-1, APP and BACE1, further reduce Aβ42 in the brains. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of Experimental Aging Research is the property of Taylor &amp; Francis Ltd and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1080/0361073X.2022.2095605
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 12
        StartPage: 214
    Subjects:
      – SubjectFull: Alzheimer's disease prevention
        Type: general
      – SubjectFull: Learning assessment
        Type: general
      – SubjectFull: Brain metabolism
        Type: general
      – SubjectFull: Protein metabolism
        Type: general
      – SubjectFull: In vitro studies
        Type: general
      – SubjectFull: Memory
        Type: general
      – SubjectFull: Animal behavior
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      – SubjectFull: In vivo studies
        Type: general
      – SubjectFull: Animal experimentation
        Type: general
      – SubjectFull: Western immunoblotting
        Type: general
      – SubjectFull: Cognition
        Type: general
      – SubjectFull: Cell receptors
        Type: general
      – SubjectFull: Low density lipoproteins
        Type: general
      – SubjectFull: Amyloid beta-protein precursor
        Type: general
      – SubjectFull: Membrane glycoproteins
        Type: general
      – SubjectFull: DNA-binding proteins
        Type: general
      – SubjectFull: Enzyme-linked immunosorbent assay
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      – SubjectFull: Research funding
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      – SubjectFull: Colorimetry
        Type: general
      – SubjectFull: High density lipoproteins
        Type: general
      – SubjectFull: Dietary fats
        Type: general
      – SubjectFull: Space perception
        Type: general
      – SubjectFull: Cholesterol
        Type: general
      – SubjectFull: Carrier proteins
        Type: general
    Titles:
      – TitleFull: 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
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            – D: 01
              M: 05
              Text: May/Jun2023
              Type: published
              Y: 2023
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