title: Liver X receptor-β improves autism symptoms via downregulation of β-amyloid expression in cortical neurons.
abstract: BACKGROUND
  We study the effect of liver X receptor β (LXRβ) on β-amyloid (Aβ) peptide generation and autism behaviors by conducting an animal experiment.
  
  
  METHODS
  In autistic mice treated with LXRβ agonist T0901317, enzyme linked immunosorbent assay was used to measure Aβ in brain tissue homogenates. Western blot was used to detect Aβ precursors, Aβ degradation and secretase enzymes, and expression of autophagy-related proteins and Ras/Raf/Erkl/2 signaling pathway proteins in brain tissue. Changes in autism spectrum disorder syndromes of the BTBR mice were compared before and after T0901317 treatment.
  
  
  RESULTS
  Compared with the control group, autistic mice treated with LXRβ agonist T0901317 showed significantly lower Aβ level in brain tissue (P < 0.05), significantly higher Aβ degradation enzyme (NEP, IDE proteins) levels (all P < 0.05), significantly lower Aβ secretase enzyme BACE1 protein level (P < 0.05), and significantly lower Ras, P-C-Raf, C-Raf, P-Mekl/2, P-Erkl/2 protein levels (all P < 0.05). BTBR mice treated with T0901317 showed improvements in repetitive stereotyped behavior, inactivity, wall-facing standing time, self-combing time and center stay time, stayed longer in platform quadrant, and crossed the platform more frequently (all P < 0.05).
  
  
  CONCLUSIONS
  LXRβ could potentially reduce brain Aβ generation by inhibiting Aβ production and promoting Aβ degradation, thereby increasing the expression of autophagy-related proteins, reducing Ras/Raf/Erkl/2 signaling pathway proteins, and improving autism behaviors.
authors.affiliation: Department of Clinical Psychology, Linyi People's Hospital, Linyi, 276000, China.
authors.forename: Ji-Xiang
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Department of Children's Rehabilitation, Linyi People's Hospital, No.27 East Jiefang Road, Linyi, 276000, China. zhangjun_linyi@yeah.net.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Outpatient Operation Room, Linyi People's Hospital, Linyi, 276000, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
mesh_terms: D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001321:Autistic Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D001343:Autophagy; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D004195:Disease Models, Animal; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D000071518:Liver X Receptors / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012016:Reference Values; D013449:Sulfonamides / Q000494:pharmacology*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
keywords: Autism; Behavioral observation; Liver X receptor; T0901317; β- amyloid protein