Wnt/β-catenin信号通路对孤独症模型大鼠重复呆板样行为的影响

doi:10.13418/j.issn.1001-165x.2015.04.012

Chinese Journal Of Clinical Anatomy ›› 2015, Vol. 33 ›› Issue (4): 430-433.doi: 10.13418/j.issn.1001-165x.2015.04.012

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Effects of Wnt/β-catenin on repetitive/stereotypic-like movements in an autistic model induced by prenatal exposure to valproic acid

ZHANG Ying-hua ^1,2, JIA Yun-jie³, ZHANG Tian-ran¹, CUI Wei-gang^{4, 1}, WANG Zhong-ping⁴, WEN Xiao-jun¹

1.Department of Human Anatomy, Xinxiang Medical University, Xinxiang 453003, China; 2.Key Laboratory for Medical Tissue Regeneration of Henan Province, College of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003; 3. Library of Xinxiang Medical University, Xinxiang 453003, China; 4.Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Received:2015-01-06 Online:2015-07-25 Published:2015-08-14

Abstract

Abstract:

Objective　To investigate the effects of Wnt/β-catenin on repetitive/stereotypic-like movements in autism. 　Methods　With an autistic model induced by prenatal exposure to valproic acid（VPA）, we detected the expression of GSK-3β, β-catenin, the signaling molecules of the canonical Wnt pathway in the cerebellum of autistic rats. The expression levels of GSK-3β, phosphorylated GSK-3β, β-catenin, phosphorylated β-catenin were observed by Western blotting. The number of repetitive/stereotypic-like behaviors and time engaged in repetitive/stereotypic-like movements were observed by open field. Results　The phospholated protein levels of GSK-3β were higher, whereas those of β-catenin were lower in VPA-exposed group than those in the control group. In contrast, the number of repetitive/stereotypic-like behaviors and time engaged in repetitive/stereotypic-like movements were significantly higher in the animals treated with VPA than those in the control group.　Conclusion　Hyperkinetics and increased activity of the canonical Wnt pathway in cerebellum of autistic rats suggest that increased activity of the canonical Wnt pathway may result in repetitive/stereotypic-like mobility disorders and further contribute to the susceptibility to autism.

Key words: Autism, Wnt/β-catenin pathway, Valproic acid, Repetitive/stereotypic-like movement

References

[1] Hattier MA, Matson JL, Macmillan K, et al. Stereotyped behaviours in children with autism spectrum disorders and atypical development as measured by the BPI-01[J]. Dev Neurorehabil, 2013,16(5):291-300.
[2] Sutera S, Pandey J, Esser EL, et al. Predictors of optimal outcome in toddlers diagnosed with autism spectrum disorders[J]. J Autism Dev Disord, 2007,37(1):98-107.
[3] Rogers TD, McKimm E, Dickson PE, et al. Is autism a disease of the cerebellum? An integration of clinical and pre-clinical research[J]. Front Syst Neurosci, 2013,7(15):1-16.
[4] Webb SJ, Sparks BF, Friedman SD, et al. Cerebellar vermal volumes and behavioral correlates in children with autism spectrum disorder[J]. Psychiatry Res, 2009,172(1):61-67.
[5] Strick PL, Dum RP, Fiez JA. Cerebellum and nonmotor function[J]. Annu Rev Neurosci, 2009,32(1):413-434.
[6] Schneider T, Przewlocki R. Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism[J]. Neuropsychopharmacology, 2005,30(1):80-89.
[7] Zeidán-Chuliá F, de Oliveira BH, Salmina AB, et al. Altered expression of Alzheimer’s disease-related genes in the cerebellumof autistic patients: amodel for disrupted brain connectome and therapy[J]. Cell Death Dis, 2014, 5( e1250):1-13.

[8] 陈明军, 于剑锋, 柴继侠, 等.Wnt通路信号蛋白β-catenin和GSK-3β在孤独症模型大鼠脑中表达的变化[J]. 神经解剖学杂志，2009，25（4）：361-368.
[9] Goldman S, O'Brien LM, Filipek PA, et al. Motor stereotypies and volumetric brain alterations in children with Autistic Disorder[J]. Res Autism Spectr Disord, 2013,7(1):82-92.
[10] Markram K, Rinaldi T, La Mendola D, et al. Abnormal fear conditioning and amygdala processing in an animal model of autism[J]. Neuropsychopharmacology, 2008,33(4):901-912.
[11] Zhang Y, Sun Y, Wang F, et al. Downregulating the Canonical Wnt/beta-catenin Signaling Pathway Attenuates the Susceptibility to Autism-like Phenotypes by Decreasing Oxidative Stress[J]. Neurochem Res, 2012,37(7):1409-1419.
[12] Tordjman S, Anderson GM, Botbol M, et al. Pain reactivity and plasma beta-endorphin in children and adolescents with autistic disorder[J]. PLoS One, 2009,4(8):e5289.

Effects of Wnt/β-catenin on repetitive/stereotypic-like movements in an autistic model induced by prenatal exposure to valproic acid

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