Are SH-SY5Y and MN9D cell lines truly dopaminergic?

Abstract

SH-SY5Y and MN9D cell lines are commonly used dopaminergic models in studies related to neurotoxicity, oxidative stress, and neurodegenerative diseases. Early studies suggested that SH-SY5Y cells do not convert intracellular DA to NE even though high levels of DβM are present in these cells. In contrast, our studies show that these cells do not store substantial levels of DA or NE, but extracellular DA is taken up and converted to NE efficiently. The efficiency of DA uptake and its conversion to NE increase with the number of cell passages. Kinetic studies show that NE is a better substrate for plasma membrane transporters than DA. In contrast to undifferentiated cells, 12-O-tetradecanoyl-phorbol- 13-acetate (TPA) differentiated SH-SY5Y cells store substantially higher levels of NE. These cells take up DA and NE more efficiently than undifferentiated cells. Therefore, differentiated and undifferentiated high passage SH-SY5Y cells could be used as a noradrenergic, but not as a dopaminergic model. MN9D cells store high levels of DA under normal growth conditions, but do not convert DA to NE. They show poor catecholamine uptake characteristics compared to undifferentiated SH-SY5Y cells, however nbutyric acid differentiated MN9D cells show efficient DA uptake kinetics similar to undifferentiated SH-SY5Y, suggesting that they could be used as a reasonable dopaminergic model.