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01.12.2016 | Research | Ausgabe 1/2016 Open Access

Italian Journal of Pediatrics 1/2016

Liver X receptor-β improves autism symptoms via downregulation of β-amyloid expression in cortical neurons

Zeitschrift:
Italian Journal of Pediatrics > Ausgabe 1/2016
Autoren:
Ji-Xiang Zhang, Jun Zhang, Ye Li
Wichtige Hinweise

Competing interests

The authors declare that they have no competing interest.

Authors’ contributions

J-XZ conceived of the study, participated in the design of the study and drafted the manuscript. JZ participated in its design and coordination and helped to draft the manuscript. YL performed the statistical analysis. All authors read and approved the final manuscript.

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.
Literatur
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