Effects of polychlorinated biphenyls (PCBs) on expression of neurotrophic factors in C6 glial cells in culture

Abstract

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that affect nervous system function. Glial cells are among the first lines of defense in the nervous system and are involved in activities, including production of neurotrophic factors, which maintain an environment optimally suited for neuronal function. In this study, we investigated the effects of a commercial mixture of PCBs, Aroclor 1254 (A1254), on neurotrophic factor secretion by C6 cells in culture. C6 cells were exposed to medium containing 10 ppm A1254, 0.1% dimethyl sulfoxide (DMSO = vehicle), or normal culture medium. Glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) protein were measured by enzyme-linked immunosorbant assay. GDNF mRNA was measured by real-time RT-PCR. The role of protein kinase C (PKC) signaling in A1254 effects was investigated using bisindolylmaleimide, a PKC antagonist. Exposure to A1254 increased NGF (8.8 × 10 −5 ± 8.2 × 10 −6 pg NGF/cell) and GDNF (1.0 × 10 −4 ± 6.7 × 10 −6 pg GDNF/cell) secretion compared to DMSO treated controls (5.0 × 10 −5 ± 7.5 × 10 −6 pg NGF/cell and 6.2 × 10 −5 ± 3.1 × 10 −6 pg GDNF/cell). The effect of A1254 was long-lived, as GDNF secretion was elevated following 5 days of exposure (4.1 × 10 −5 ± 1.7 × 10 −6 pg GDNF/cell in A1254 exposed cells vs. 2.9 × 10 −5 ± 2.3 × 10 −6 pg GDNF/cell in DMSO exposed cells). GDNF mRNA expression was also elevated following exposure to A1254 (1.14 ± 0.07 gene expression units in A1254 exposed cells vs. 0.8 ± 0.07 gene expression units in DMSO exposed cells). Bisindolylmaleimide was able to block the effects of A1254 on GDNF secretion. Thus, one potential mechanism by which PCBs may alter nervous system function is via disruption of neurotrophic factor expression by glial cells. The observation that neurotrophic factor expression was increased following exposure to PCB may suggest that glial cells increase expression of neuroprotective genes following exposure to potentially damaging agents such as PCBs.