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

Previous Articles     Next Articles

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

PDF (PC)

348

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
[1] Stacy M. Medical treatment of Parkinson disease[J]. Neurol Clin, 2009, 27(3): 605-631.
[2] Lin LF, Doherty DH, Lile JD, et al. GDNF: a glial cell line derived neurotrophic factor for midbrain dopaminergic neurons[J]. Science, 1993, 260(5111): 1130-1132.
[3] Lu-Nguyen NB, Broadstock M, Schliesser MG, et al. Transgenic expression of human glial cell line-derived neurotrophic factor from integration-deficient lentiviral vectors is neuroprotective in a rodent model of Parkinsons disease[J]. Hum Gene Ther, 2014, 25(7): 631-641.
[4] Gash DM, Zhang Z, Ovadia A, et al. Functional recovery in parkinsonian monkeys treated with GDNF[J]. Nature, 1996, 380(6571): 252-255.
[5] Cohen AD, Zigmond MJ, Smith AD, et al. Effects of intrastriatal GDNF on the response of dopamine neurons to 6-hydroxydopamine: Time course of protection and neurorestoration[J]. Brain Res, 2011, 1370(2011): 80-88.
[6] 刘洪梅, 丁艳霞, 王炎强, 等. 表皮生长因子加强胶质细胞系源性神经营养因子对PD 模型大鼠黑质多巴胺能神经元的保护作用[J]. 解剖学杂志, 2011, 34(5): 537-575. LIU Hongmei, DING Yanxia, WANG Yanqiang, et al. EGF enhances the effect of GDNF on protecting dopamine neurons in substantia nigra of Parkinsons disease model in rats[J]. Chinese Journal of Anatomy, 2011, 34(5): 537-575.
[7] Gonzalez-Aparicio R, Flores JA, Fernandez-Espejo E. Antiparkinsonian trophic action of glial cell line-derived neurotrophic factor and transforming growth factor β1 is enhanced after co-infusion in rats[J]. ExpNeurol, 2010, 226(1): 136-147.
[8] Dunnett SB, Carter RJ, Watts C, et al. Striatal transplantation in a transgenic mouse model of Huntington's disease[J]. ExpNeurol, 1998, 154(1): 31-40.
[9] Ogawa N, Hirose Y, Ohara S, et al. A simple quantitative bradykinesia test in MPTP-treated mice[J]. Res Commun Chem Pathol Pharmacol, 1985, 50(3): 435-441.
[10] Olsson M, Nikkhah G, Bentlage C, et al. Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test[J]. J Neurosci, 1995, 15(2): 3863-3875.
[11] Wesson DW, Wilson DA. Age and gene overexpression interact to abolish nesting behavior in Tg2576 amyloid precursor protein(APP)mice[J]. Behav Brain Res, 2011, 216(1): 408-413.
[12] Tomac A, Lindqvist E, Lin LF, et al.Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo[J]. Nature, 1995, 373(6512): 335-339.
[13] Bernheimer H, Birkmayer W, Hornykiewicz O, et al. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations[J]. J Neurol Sci, 1973, 20(4): 415-455.
[14] Littrell OM, Granholm AC, Gerhardt GA, et al. Glial cell-line derived neurotrophic factor(GDNF)replacement attenuates motor impairments and nigrostriatal dopamine deficits in 12-month-old mice with a partial deletion of GDNF[J]. Pharmacol Biochem Behav, 2013, 104(3): 10-19.
[15] Tereshchenko J, Maddalena A, Bähr M, et al. Pharmacologically controlled, discontinuous GDNF gene therapy restores motor function in a rat model of Parkinsons disease[J]. Neurobiol Dis, 2014, 65(5): 35-42.
[16] Cash R, Raisman R, Ploska A, et al. High and low affinity[3H] imipramine binding sites in control and parkinsonian brains[J]. Eur J Pharmacol, 1985, 117(1): 71-80.
[17] Lelieveld IM, Müller ML, Bohnen NI, et al. The role of serotonin in sleep disordered breathing associated with Parkinson disease: a correlative[11C] DASB PET imaging study[J]. PLoS One, 2012, 7(7): e40166.
[18] Biju K, Zhou Q, Li G, et al. Macrophage-mediated GDNF delivery protects against dopaminergic neurodegeneration: a therapeutic strategy for Parkinsons disease[J]. Molecular Therapy, 2010, 18(8): 1536-1544.
[19] Pardo J, Morel GR, Astiz M, et al. Gene Therapy and Cell Reprogramming for the Aging Brain: Achievements and Promise[J]. Curr Gene Ther, 2014, 14(1): 24-34.
[20] Lu-Nguyen NB, Broadstock M, Schliesser MG, et al. Transgenic expression of human glial cell line-derived neurotrophic factor from integration-deficient lentiviral vectors is neuroprotective in a rodent model of Parkinson's disease[J]. Hum Gene Ther, 2014, 25(7): 631-641.
[1] ZHANG Shi-Bao, LIU Qing-Yong, RUAN Xi-Yun, CHEN Jie, ZHANG Jian-Jun, LI Zong-Wu, YANG Guang-Xiao, WANG Quan-Ying. onstruction and identification of the expression vector of
NT4-SAC-HA2-TAT fusion gene [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 15-19.
[2] LIU Dong, ZHU Dongyun, PENG Changliang, ZHANG Cheng, ZHAO Jie, GAO Chunzheng. Construction and appraisal of hyaluronic acid hydrogel scaffold in the treatment of treat spinal cord injury [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(9): 53-59.
[3] ZHANG Xinke, CHEN Hongyuan, YANG Ying, LI Yan, WANG Fengshan. Development and evaluation of chitosan gene nanoparticles loaded with recombinant plasmid pVAX1/Tat PTD-endostatin [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(7): 43-48.
[4] ZHANG Wen1, FENG Tingting1, ZHENG Lin1, WANG Hong1, LU Yi2, QI Mei1, YU Xiuping1, TANG Wei1, ZHAO Weiming1. Effects of enhanced expression of RbAp48 mediated by recombinant adenovirus on proliferation and growth of cervical cancer cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(4): 13-17.
[5] ZHANG Bin1, CHEN Jie2, LIU Yan3, ZHANG Shi-bao2, LIU Shuang-qing2, LIU Bo2,WANG Quan-ying4, YANG Guang-xiao4, LIU Qing-yong2. Anti-tumor effect of recombinant adeno-associated virus mediated secretive expression of renal cell carcinoma suppressor fusion peptide on chick embryo implanted tumors [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(5): 33-36.
[6] SUN Yan-lai1, SONG Xi-lin2, TANG Lu-bing3， WANG Bin1, ZHANG Yi1. Effects of BRMS1 on tumorigenicity and metastasis of
human rectal cancer cells in nude mice [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(9): 25-.
[7] YU Zhang-jian1, ZHANG Shi-bao1, LIU Qing-yong1, RUAN Xi-yun2, YANG Guang-xiao3, WANG Quan-ying3. Construction of a recombinant adenoassociated viral vector expressing SAC and its inhibition on CAM xenograft prostate cancer [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(7): 41-.
[8] WANG Xiao-ping, ZHANG Rui-bin, ZHU Bin, GAO Qing-zhen,JING Yong-sheng, REN Wan-jun, WANG Pu, WANG Qi. The construction of MHC-Ⅰ intrabody recombinant AAV vector [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(12): 37-.
[9] ZHANG Wen-hua, WU Cheng-yuan, LI Xin-gang, XU Shu-jun, LI Gang, JIANG Yu-quan, ZHOU Mao-de, LIU Meng . Gene therapy for amyotrophic lateral sclerosis in  a mouse model using a human glial cell linederived neurotrophic factor [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2011, 49(11): 25-29.
[10] ZHANG Feng-wei1, WU Shu-ming2, CAO Guang-qing2, LU Xian-shuo2. eNOS gene transfection on pulmonary artery hypertensionand hypertension crisis in rabbits [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(9): 19-24.
[11] KONG Shuai， LI Leping， JING Changqing, WANG Feng. The reversal effect on MDR1 gene-mediated multidrug resistance in human colon carcinoma LoVo/5-Fu cells by RNA interference [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(6): 80-83.
[12] ZHANG Jing, WANG Kun, YANG Lingling, DUAN Shan, CUI Xing. Inhibitory effects of NEP mediated by adenovirus vector on amyloid beta peptide-induced SK-N-SH cell apoptosis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(3): 48-52.
[13] TAN Wanye1, SUN Mingxia1,　PENG Huahai1, WANG Ketao1,　WEI Fengcai1,　SUN Shanzhen2. Effect of fetal rat fibroblasts on wound healing of deep second degree scalds treated with dermabrasion [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(2): 76-.
[14] CHEN Feng1, HE Shengsong1, WU Meimei1, QIU Rongyuan1, YANG Kaikai1, WANG Peng2. Comparison of different non-viral transfection methods for GFP plasmid expression in the liver of mice [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(1): 17-20.
[15] FENG Xiaoli1, ZHU Xiaobo1，2, CHEN Ou3, SU Hong1, MA Yu1, WANG Yibiao1. Effect of adenovirusmediated human endothelial nitric oxide synthase gene transfection on pulmonary hypertension rat model induced by high pulmonary blood flow [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(1): 70-73.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd