Exposure to environmental toxicants is prevalent, hazardous and linked to varied detrimental health outcomes and disease. Polychlorinated biphenyls (PCBs), a class of hazardous organic chlorines once widely used for industrial purposes, are associated with neurodegenerative disease and oxidative stress in both in vitro and in vivo models. Here, we investigated the impact of Aroclor 1254, a commercially available PCB mixture, on primary murine astrocytes to determine the response to this once ubiquitously used toxicant on the most numerous cells of the central nervous system (CNS). Astrocytes are a critical component of homeostasis throughout the CNS, including at the blood-brain barrier, where they serve as the primary defense against xenobiotics entering the CNS, and at the synapse, where they are closely coupled to neurons through several metabolic pathways. We hypothesized that PCBs cause astrocytic oxidative stress and related dysfunction including altered metabolism. We exposed primary murine cortical astrocytes to PCBs and report an increased expression of antioxidant genes (Prdx1, Gsta2, Gfap, Amigo2) in response to oxidative stress. Our data show increased ATP production and spare respiratory capacity in astrocytes exposed to 10 μM (∼ 3 ppm) PCBs. This dose also causes an increase in glucose uptake that is not seen at a higher dose (50 μM) suggesting that, at a lower dose, astrocytes are able to engage compensatory mechanisms to promote survival. Together, these data suggest that exposure to PCBs impact astrocytic metabolism, which is important to consider both in the context of human health and disease and in in vitro and in vivo disease models.

接触环境毒物是普遍存在的、危险的，并且与各种有害的健康结果和疾病有关。多氯联苯 (PCB) 是一类曾经广泛用于工业用途的有害有机氯，在体外和体内模型中都与神经退行性疾病和氧化应激有关。在这里，我们研究了 Aroclor 1254（一种市售 PCB 混合物）对原代鼠星形胶质细胞的影响，以确定这种曾经普遍使用的毒物对中枢神经系统 (CNS) 数量最多的细胞的反应。星形胶质细胞是整个中枢神经系统稳态的关键组成部分，包括在血脑屏障处，它们是防止外源物质进入中枢神经系统的主要防御手段；在突触处，它们通过多种代谢途径与神经元紧密耦合。我们假设 PCB 会导致星形胶质细胞氧化应激和相关功能障碍，包括代谢改变。我们将原代小鼠皮质星形胶质细胞暴露于多氯联苯，并报告抗氧化基因（ Prdx1、Gsta2、Gfap、Amigo2 ）的表达增加以应对氧化应激。我们的数据显示，暴露于 10 μM (∼ 3 ppm) PCB 的星形胶质细胞中 ATP 产量和备用呼吸能力有所增加。该剂量还会导致葡萄糖摄取增加，而在较高剂量 (50 μM) 下则不会出现这种情况，这表明在较低剂量下，星形胶质细胞能够参与补偿机制以促进存活。总之，这些数据表明，接触多氯联苯会影响星形细胞代谢，这在人类健康和疾病背景以及体外和体内疾病模型中都很重要。