JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2016, Vol. 54 ›› Issue (4): 32-36.doi: 10.6040/j.issn.1671-7554.0.2015.1321

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Neuroprotective effect of adenovirus-mediated GDNF gene in mice models of Parkinsons disease

WANG Si1,2, LI Xiuhua2, DU Juan3, YUE Longtao3, WANG Yao3, LIU Fei2, GUO Pei1,2   

  1. 1. Weifang Medical University, Weifang 261000, Shandong, China;
    2. Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China;
    3. Central Laboratory, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China
  • Received:2015-12-22 Online:2016-04-10 Published:2016-04-10

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Abstract: Objective To investigate the neuroprotective effect of adenovirus-mediated glial cell line-derived neurotrophic factor(GDNF)gene intracerebrally transferred on the treatment of Parkinsons disease(PD). Methods PD models were established by intraperitoneal injection of 1-methyl-4-henyl-l,2,3,6-tetrahydropyridine(MPTP)［30 mg/(kg·d)in C57Bl/6 mice. The models were then divided into Ad-GDNF experimental group and control group. Ad-GDNF was injected into the lateral ventricle of mice in the experimental group. Negative virus was injected into the lateral ventricle of mice in the control group. The body weight of all mice was measured. The neuroprotective effect of Ad-GDNF was evaluated with behavioral tests, immune histochemical assay of the tyrosine hydroxylase(TH)-positive neurons in the substance nigra and measurement of monoamine level in the striatum. The expression of the exogenous GDNF gene in the brain was detected with ELISA and RT-PCR. Results Compared with control group, the experimental group showed improved motor functions(P<0.01)and less loss of body weight(P<0.05), better survival of TH-positive cells(P<0.05), higher DA levels(P<0.05)after two weeks of intracerebroventricular injection. The exogenous 山 东 大 学 学 报 (医 学 版)54卷4期 -王思,等.侧脑室注射腺病毒介导的GDNF基因对帕金森病的保护作用 \=-GDNF gene was efficiently over expressed in the experimental group. GDNF protein level in midbrain of the experimental group was twice of the control group. Conclusion Intracerebroventricular injection of adenovirus mediated GDNF gene significantly can protect the dopaminergic neurons of nigrostriatal system from MPTP-induced injury and is conducive in the treatment of Parkinsons disease.

Key words: Glial cell line-derived neurotrophic factor, Adenovirus, Parkinsons disease, Gene therapy, 1-methyl-4-henyl-l,2,3,6-tetrahydropyridine

CLC Number: 

  • R741.02
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