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Identification and characterization of a novel neurotrophic factor secreted by a mouse Schwann cell line Xu, Ren Y.

Abstract

During development, neurotrophic factors regulate morphologic and functional differentiation in addition to their role as regulators of neuronal survival. Schwann cells are the major glial elements in the peripheral nervous system and, therefore, could play a major functional role in supporting neuronal differentiation and survival in nervous system. Here, we have characterized a neurotrophic factor secreted by MS1 cells from an immortalized Schwann cell line. In our mesencephalic culture system, a 2.9-fold increased survival of TH+ neurons at day 5 and a 1.9-fold increase of dopamine uptake have been observed when the cells were treated with MS1 conditioned medium (MCM). This trophic effect is more potent than other known trophic factors for dopaminergic neurons such as bFGF, insulin, and EGF. The characteristics of this factor are different from all other known neurotrophic factors in vitro. Partial purification of MCM has shown that the molecular weight of this factor is between 17 kDa and 30 kDa. It is a heat sensitive, non-heparin binding, protease digestible protein-like molecule. MCM did not have any mitogenic effects on astrocytes in our culture, nor did it have survival effects on 1-day-old dorsal root ganglia or E13 spinal cord culture. Thus, we conclude that the trophic factor in MCM is a novel and specific survival factor for dopaminergic neurons.

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