TRANSGENIC ACETYLCHOLINESTERASE INDUCES ENLARGEMENT OF MURINE NEUROMUSCULAR-JUNCTIONS BUT LEAVES SPINAL-CORD SYNAPSES INTACT

Acetylcholinesterase (AChE) produced by spinal cord motoneurons accumu lates within axo-dendritic spinal cord synapses. II is also secreted f rom motoneuron cell bodies, through their axone, into the region of ne uromuscular junctions. where it terminates cholinergic neurotransmissi on. Here we show that transgenic mice expressing human AChE in their s pinal cord motoneurons display primarily normal axo-dendritic spinal c ord cholinergic synapses in spite of the clear excess of transgenic ov er host AChE within these synapses. This is in contrast to our recent observation that a modest excess of AChE drastically affects the struc ture and longterm functioning of neuromuscular junctions in these mice although they express human AChE in their spinal cord, but not muscle . Enlarged muscle endplates with either exaggerated or drastically sho rtened post-synaptic folds then lead to a progressive neuromotor decli ne and massive amyotrophy (Andres et al., 1997). These findings demons trate that excess neuronal AChE may cause distinct effects on spinal c ord and neuromuscular synapses and attribute the late-onset neuromotor deterioration observed in AChE transgenic mice to neuromuscular junct ion abnormalities. (C) 1998 Elsevier Science Ltd. All rights reserved.