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首页> 中文期刊> 《转化神经变性病(英文)》 >Alpha-synuclein overexpression in the olfactory bulb initiates prodromal symptoms and pathology of Parkinson’s disease

Alpha-synuclein overexpression in the olfactory bulb initiates prodromal symptoms and pathology of Parkinson’s disease

         
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摘要

Background:Parkinson’s disease(PD)is a neurodegenerative disease characterized by intraneuronal Lewy Body(LB)aggregates composed of misfolded alpha-synuclein(α-syn).The spread of misfoldedα-syn follows a typical pattern:starting in the olfactory bulb(OB)and the gut,this pathology is followed by the progressive invasion of misfoldedα-syn to the posterior part of the brain.It is unknown whether the administration of human mutant alpha-synuclein(hm-α-syn,a human mutation which occurs in familial PD)into the OB of rats would trigger similarα-syn propagation and subsequently cause pathological changes in broader brain fields associated to PD and establish an animal model of prodromal PD.Methods:hm-α-syn was overexpressed in the OB of rats with an AAV injection.Then motor and non-motor symptoms of the SD rats were tested in different behavioral tasks following the AAV injection.In follow-up studies,pathological mechanisms ofα-syn spread were explored at the histological,biochemical and micro-structure levels.Results:The experimental results indicated that hm-α-syn was overexpressed in the OB 3 weeks after the AAV injection.1)overexpression of the Hm-α-syn in the OB by the AAV injection could transfer to wider adjacent fields beyond the monosynaptic scope.2)The number of tyrosine hydroxylase positive cells body and fibers was decreased in the substantia nigra(SN)12 weeks after AAV injection.This was consistent with decreased levels of the DA neurotransmitter.Importantly,behavioral dysfunctions were found that included olfactory impairment after 3 weeks,motor ability impairment and decreased muscular coordination on a rotarod 6 weeks after the AAV injection.3)The morphological level studies found that the Golgi staining revealed the number of neuronal branches and synapses in the OB,prefrontal cortex(PFC),hippocampus(Hip)and striatum caudate putamen(CPU)were decreased.4)phosphorylatedα-syn,at Ser-129(pSer129),was found to be increased in hm-α-syn injected animals in comparison to controls that overexpressed GFP alone,which was also found in the most of LB stained by the thioflavine S(ThS)in the SN field.5)A marker of autophagy(LC3B)was increased in serval fields,which was colacolizated with a marker of apoptosis in the SN field.Conclusions:These results demonstrate that expression of exogenous mutantα-syn in the OB induces pathological changes in the sensitive brain fields by transferring pathogenicα-syn to adjacent fields.This method may be useful for establishing an animal model of prodromal PD.

著录项

  • 来源
    《转化神经变性病(英文)》 |2018年第1期|P.244-260|共17页
  • 作者

    Haichen Niu; Lingyu Shen; Tongzhou Li; Chao Ren; Sheng Ding; Lei Wang; Zhonghai Zhang; Xiaoyu Liu; Qiang Zhang; Deqin Geng; Xiujuan Wu; Haiying Li;

  • 作者单位

    Department of Genetics Xuzhou Medical University Xuzhou 221004 China;

    Department of Epidemiology and Health Statistics Xuzhou Medical University Xuzhou 221004 China;

    Department of Epidemiology and Health Statistics Xuzhou Medical University Xuzhou 221004 China;

    Department of Neurology Affiliated Yantai Yuhuangding Hospital of Qingdao University Yantai 264000 China;

    Department of Epidemiology and Health Statistics Xuzhou Medical University Xuzhou 221004 China;

    Department of Genetics Xuzhou Medical University Xuzhou 221004 China;

    Department of Genetics Xuzhou Medical University Xuzhou 221004 China;

    College of Medicine Institute for Behavioral Medicine Research The Ohio State University Columbus OH USA;

    Department of Genetics Xuzhou Medical University Xuzhou 221004 China;

    Department of Neurology Affiliated Hospital of Xuzhou Medical University Xuzhou 221004 China;

    Department of Epidemiology and Health Statistics Xuzhou Medical University Xuzhou 221004 China;

    Department of Pathology Xuzhou Medical University Xuzhou 221004 China;

  • 原文格式 PDF
  • 正文语种 chi
  • 中图分类 肿瘤学;
  • 关键词

    Alpha-synuclein; Prodromal; animal; model; Parkinson’s; disease; Olfactory; bulb; Autophagy;

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