Bcl-2 and GDNF delivered by HSV-Mediated Gene Transfer Act additively to protect dopaminergic neurons from 6-OHDA-induced degeneration
Bcl-2 and GDNF delivered by HSV-Mediated Gene Transfer Act additively to protect dopaminergic neurons from 6-OHDA-induced degeneration
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DOI：
10.1006/exnr.2001.7671
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发表时间：
2001-06-01
影响因子：
5.3
通讯作者：
Fink, DJ
中科院分区：
文献类型：
--
作者：
Natsume, A;Mata, M;Fink, DJ
以往的研究表明，无论是神经营养因子胶质源性神经营养因子(GDNF)还是由病毒载体导入纹状体内的抗细胞凋亡肽Bcl2，都能保护黑质多巴胺能神经元免受神经毒素g-羟基多巴胺(6-OHDA)诱导的变性。在本研究中，我们使用复制不能的基因组单纯疱疹病毒载体在6-OHDA注射前一周将编码Bcl2和GDNF的基因导入大鼠黑质(SN)。荧光金(FG)逆行标记显示，单独表达Bcl2或GDNF后，损伤侧SN细胞存活率增加一倍，酪氨酸羟基酶免疫反应(TH-IR)神经元增加50%。基因转移的Bcl2和GDNF在这方面的作用相当。通过FG标记和TH-IR的表达，联合应用Bcl2表达载体和GDNF表达载体可使受损黑质神经元的存活率提高33%和15%。这些结果表明，在面对6-OHDA毒性时，这两个因素共同作用，以相加的方式提高DA细胞的存活率。(C)2001年学术出版社。
Previous studies have demonstrated that either the neurotrophin glial-derived neurotrophic factor (GDNF) or the antiapoptotic peptide Bcl-2 delivered into striatum by a viral vector protects dopaminergic neurons of the substantia nigra in vivo from degeneration induced by the administration of the neurotoxin g-hydroxydopamine (6-OHDA), In this study we used recombinant, replication-incompetent, genomic herpes simplex virus-based vectors to deliver the genes coding for Bcl-2 and GDNF into rat substantia nigra (SN) 1 week prior to 6-OHDA injection into the striatum. Vector-mediated expression of either Bcl-2 or GDNF alone each resulted in a doubling in cell survival as measured by retrograde labeling with fluorogold (FG) and a 50% increase in tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the lesioned SN compared to the unlesioned side. Gene transfer of Bcl-2 and GDNF were equivalent in this effect. Coadministration of the Bcl-2-expressing vector with the GDNF-expressing vector improved the survival of lesioned SN neurons as measured by FG labeling by 33% and by the expression of TH-IR by 15%. These results suggest that the two factors delivered together act in an additive fashion to improve DA cell survival in the face of 6-OHDA toxicity. (C) 2001 Academic Press.