Abstract

The long term aim of this study is to understand the regulation of glial cell line‐derived neurotrophic factor (GDNF) at the neuromuscular junction (NMJ). GDNF has been identified as a potent survival factor for both central and peripheral neurons. Although the effects of exogenous administration of GDNF at the NMJ have been extensively studied, little is known about factors that regulate intracellular GDNF expression and secretion. In this study a coculture system of the C2C12 skeletal muscle cell line and the NG108‐15 neural cell line was used. GDNF protein within cells and in conditioned cell culture medium was analyzed by Enzyme‐Linked Immunosorbant assay. GDNF localization was examined by immonohistochemical analysis. The results showed that addition of acetylcholine (ACh) to cultured skeletal muscle cells inhibited GDNF secretion by skeletal muscle. The nerve‐muscle coculture study indicated that the addition of motoneurons to skeletal muscle cells also reduced the secretion of GDNF by skeletal muscle. The results suggest that motoneurons may be regulating their own supply of GDNF being produced by skeletal muscle, possibly via ACh release. This work was supported by NIH grant 1 R15 AG022908‐01A2, Western Michigan University, and MSU‐KCMS.

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