1,3-Dinitrobenzene neurotoxicity - Passage effect in immortalized astrocytes.
1,3-Dinitrobenzene neurotoxicity - Passage effect in immortalized astrocytes.
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DOI：
10.1016/j.neuro.2015.11.011
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发表时间：
2016-03
期刊：
影响因子：
3.4
通讯作者：
Philbert MA
中科院分区：
文献类型：
--
作者：
Maurer LL;Latham JD;Landis RW;Song DH;Epstein T;Philbert MA
星形胶质细胞线粒体功能中的神经保护相关紊乱与神经功能的丧失和减退有关。永生化大鼠新皮层星形胶质细胞衍生的细胞系，DI-TNC 1，提供了一个方便的模型，用于检查细胞衰老过程，这是很难研究的主要细胞分离老年脑。培养物中的连续传代可作为老化的替代物，其中对培养条件的时间依赖性适应可导致对外源性挑战的反应改变。为了研究星形胶质细胞线粒体稳态功能在培养中随时间降低的假设，将低传代DI-TNC 1星形胶质细胞（LP; #2-8）和高传代DI-TNC 1星形胶质细胞（HP; #17- 2 - 8）暴露于线粒体神经毒物1，3-二硝基苯（DNB）。将细胞暴露于单一培养物或与原代皮层神经元共培养物中。星形胶质细胞的线粒体膜电位，形态，ATP的生产和增殖进行了监测，在单培养，和缓冲K+诱导的神经元去极化的能力的DI-TNC 1细胞进行了检查，在共培养。在HP DI-TNC 1细胞中，DNB暴露降低了增殖，降低了线粒体膜电位，并显著降低了线粒体形状因子。低代DI-TNC 1细胞在DNB存在下有效地减弱K+诱导的神经元去极化，而HP对应物在DNB挑战中不能缓冲K+。在DNB攻击后，LP DI-TNC 1细胞在共培养中表现出比HP更大的活力。数据提供了令人信服的证据，即在第9 -16代之间，DI-TNC 1细胞中存在突然的表型变化，其显著降低了DI-TNC 1细胞补偿神经毒性攻击和提供神经保护性空间缓冲的能力。这些功能变化是否在衰老的大脑中具有体内类似物仍有待确定。
Age-related disturbances in astrocytic mitochondrial function are linked to loss of neuroprotection and decrements in neurological function. The immortalized rat neocortical astrocyte-derived cell line, DI-TNC1, provides a convenient model for the examination of cellular aging processes that are difficult to study in primary cell isolates from aged brain. Successive passages in culture may serve as a surrogate of aging in which time-dependent adaptation to culture conditions may result in altered responses to xenobiotic challenge. To investigate the hypothesis that astrocytic mitochondrial homeostatic function is decreased with time in culture, low passage DI-TNC1 astrocytes (LP; #2–8) and high passage DI-TNC1 astrocytes (HP; #17–28) were exposed to the mitochondrial neurotoxicant 1,3-dinitrobenzene (DNB). Cells were exposed in either monoculture or in co-culture with primary cortical neurons. Astrocyte mitochondrial membrane potential, morphology, ATP production and proliferation were monitored in monoculture, and the ability of DI-TNC1 cells to buffer K+-induced neuronal depolarization was examined in co-cultures. In HP DI-TNC1 cells, DNB exposure decreased proliferation, reduced mitochondrial membrane potential and significantly decreased mitochondrial form factor. Low passage DI-TNC1 cells effectively attenuated K+-induced neuronal depolarization in the presence of DNB whereas HP counterparts were unable to buffer K+ in DNB challenge. Following DNB challenge, LP DI-TNC1 cells exhibited greater viability in co-culture than HP. The data provide compelling evidence that there is an abrupt phenotypic change in DI-TNC1 cells between passage #9–16 that significantly diminishes the ability of DI-TNC1 cells to compensate for neurotoxic challenge and provide neuroprotective spatial buffering. Whether or not these functional changes have an in vivo analog in aging brain remains to be determined.
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