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首页> 外文期刊>The European Journal of Neuroscience >Expression of BCL-2 via adeno-associated virus vectors rescues thalamic neurons after visual cortex lesion in the adult rat.
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Expression of BCL-2 via adeno-associated virus vectors rescues thalamic neurons after visual cortex lesion in the adult rat.

机译：BCL-2通过腺相关病毒载体的表达在成年大鼠视觉皮层损伤后拯救了丘脑神经元。

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摘要

Lesions of the mammalian visual cortex cause the retrograde degeneration of the thalamic neurons projecting to the damaged cortex. The proto-oncogene bcl-2 is known to inhibit neuronal apoptosis induced by a variety of noxious stimuli and preserve the functional integrity of the injured cells. Here we have tested whether the overexpression of bcl-2 via adeno-associated virus (AAV) vectors is able to protect the neurons in the lateral geniculate nucleus after visual cortex ablation in adult rats. Recombinant AAV vectors encoding Bcl-2 (AAV-Bcl-2) or green fluorescent protein (AAV-GFP) as a control were stereotaxically injected into the geniculate. Three weeks after vector injection, the ipsilateral visual cortex was removed by aspiration, and cell survival was assessed 2 weeks later. We found that 20% of the geniculate neurons were transduced by the Bcl-2 vector. These cells were completely protected from death following cortical ablation. Delivery of AAV-GFP transduced an identical number of geniculate neurons but had no effect on cell survival after lesion. The total number of surviving geniculate neurons was found to be significantly higher in animals injected with AAV-Bcl-2 than in rats injected with AAV-GFP or in control lesioned rats. These data indicate that Bcl-2 gene therapy with AAV vectors represents an effective treatment to promote neuronal survival after central nervous system insults.
机译：哺乳动物视觉皮层的损伤导致丘脑神经元逆行变性，突出到受损的皮层。已知原癌基因bcl-2抑制多种有害刺激诱导的神经元凋亡，并保留受损细胞的功能完整性。在这里，我们测试了成年大鼠视觉皮层消融后通过腺相关病毒（AAV）载体过表达bcl-2是否能够保护外侧膝状核中的神经元。将编码Bcl-2（AAV-Bcl-2）或绿色荧光蛋白（AAV-GFP）作为对照的重组AAV载体立体定向注射到膝状体中。注射载体三周后，通过抽吸去除同侧视皮层，并在2周后评估细胞存活率。我们发现Bcl-2载体转导了20％的膝状神经元。皮质消融后，这些细胞被完全保护免受死亡。 AAV-GFP的传递转导相同数目的膝状神经元，但对病变后的细胞存活没有影响。发现在注射AAV-Bcl-2的动物中存活的膝状神经元的总数显着高于注射AAV-GFP的大鼠或在对照病变大鼠中。这些数据表明，用AAV载体进行的Bcl-2基因治疗代表了一种促进中枢神经系统损伤后神经元存活的有效治疗方法。

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