The HIV Protein gp120 Alters Mitochondrial Dynamics in Neurons.
The HIV Protein gp120 Alters Mitochondrial Dynamics in Neurons.
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DOI：
10.1007/s12640-016-9608-6
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发表时间：
2016-05
影响因子：
3.7
通讯作者：
Mocchetti I
中科院分区：
文献类型：
--
作者：
Avdoshina V;Fields JA;Castellano P;Dedoni S;Palchik G;Trejo M;Adame A;Rockenstein E;Eugenin E;Masliah E;Mocchetti I
人类免疫缺陷病毒1型（HIV）的神经毒性包括突触简化和神经元凋亡。然而，HIV相关神经毒性的机制仍不清楚，从而排除了神经系统并发症的有效治疗。本研究旨在描述HIV神经毒性的新机制，这可能解释HIV受试者如何发生神经元变性。一些神经退行性疾病的特点是线粒体功能障碍，因此，我们假设，艾滋病毒促进线粒体损伤。我们首先通过电子显微镜分析了艾滋病毒脑炎（HIVE）的大脑。与没有神经系统并发症的HIV受试者的大脑相比，HIVE受试者的几个切片含有扩大和受损的线粒体。在过表达HIV蛋白gp120的小鼠中观察到类似的病理学，表明这种病毒蛋白可能是HIVE中发现的线粒体病理学的原因。为了获得更多关于gp120神经毒性细胞机制的信息，我们将大鼠皮层神经元暴露于gp120，并测定细胞耗氧率、线粒体分布和运输。我们的数据表明，gp120引起线粒体功能和分布的损害。这些数据表明，HIV神经毒性的机制之一包括改变神经元中的线粒体动力学。
Neurotoxicity of human immunodeficiency virus-1 (HIV) includes synaptic simplification and neuronal apoptosis. However, the mechanisms of HIV-associated neurotoxicity remain unclear, thus precluding an effective treatment of the neurological complications. The present study was undertaken to characterize novel mechanisms of HIV neurotoxicity that may explain how HIV subjects develop neuronal degeneration. Several neurodegenerative disorders are characterized by mitochondrial dysfunction; therefore, we hypothesized that HIV promotes mitochondrial damage. We first analyzed brains from HIV encephalitis (HIVE) by electron microscopy. Several sections of HIVE subjects contained enlarged and damaged mitochondria compared to brains from HIV subjects with no neurological complications. Similar pathologies were observed in mice overexpressing the HIV protein gp120, suggesting that this viral protein may be responsible for mitochondrial pathology found in HIVE. To gain more information about the cellular mechanisms of gp120 neurotoxicity, we exposed rat cortical neurons to gp120 and we determined cellular oxygen consumption rate, mitochondrial distribution, and trafficking. Our data show that gp120 evokes impairment in mitochondrial function and distribution. These data suggest that one of the mechanisms of HIV neurotoxicity includes altered mitochondrial dynamics in neurons.