Document Type

Poster

Publication Date

2008

Abstract

Glialcell line-derived neurotrophicfactor (GDNF) has been regarded as a potent survival factor for a subpopulation of neurons. It has been shown that GDNF expression is upregulated in skeletal muscle of patients with early stage of neuromuscular diseases such as amyotrophic lateral sclerosis (ALS). Previous results from our laboratory showed that neural cells regulate GDNF secretion by skeletal muscle; non-innervated skeletal muscle appear to secrete more GDNF compared to innervated skeletal muscle. Two aims were examined in the current study. First, to examine whether neural cells inhibit GDNF through acetylcholine release. Second was to examine whether differentiated NG108-15 neural cells secrete GDNF. Acetylcholine receptors on nerve-muscle co-cultured cells were blocked with alpha bungarotoxin(-BTX). Results showed that -BTX reversed the action of neural cells, suggesting that neural cells regulate GDNF production through acetylcholine release. ELISA results showed no GDNF in differentiated NG108-15 cells grown alone. However, immunocytochemistryresults showed that GDNF was localized in NG108-15 cells co-cultured with myotubes. These observations suggest that upon contact, cholinergic neural cells not only regulate GDNF secretion but also may be utilizing GDNF secreted by skeletal muscle. Taken together, our results suggest that cholinergic neural cells depend on and regulate GDNF secreted by its target. Supported byNIH Grant 1R15AG022908-01A2, MSU-KCMS, and Western Michigan University.