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Molecules 2017, 22(9), 1418; doi:10.3390/molecules22091418

In Vitro Innervation as an Experimental Model to Study the Expression and Functions of Acetylcholinesterase and Agrin in Human Skeletal Muscle

1
Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, SI-1000 Ljubljana, Slovenia
2
Department of Life Sciences, University of Trieste, via A. Fleming 22, I-34127 Trieste, Italy
*
Authors to whom correspondence should be addressed.
Received: 24 July 2017 / Revised: 18 August 2017 / Accepted: 23 August 2017 / Published: 27 August 2017
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Abstract

Acetylcholinesterase (AChE) and agrin, a heparan-sulfate proteoglycan, reside in the basal lamina of the neuromuscular junction (NMJ) and play key roles in cholinergic transmission and synaptogenesis. Unlike most NMJ components, AChE and agrin are expressed in skeletal muscle and α-motor neurons. AChE and agrin are also expressed in various other types of cells, where they have important alternative functions that are not related to their classical roles in NMJ. In this review, we first focus on co-cultures of embryonic rat spinal cord explants with human skeletal muscle cells as an experimental model to study functional innervation in vitro. We describe how this heterologous rat-human model, which enables experimentation on highly developed contracting human myotubes, offers unique opportunities for AChE and agrin research. We then highlight innovative approaches that were used to address salient questions regarding expression and alternative functions of AChE and agrin in developing human skeletal muscle. Results obtained in co-cultures are compared with those obtained in other models in the context of general advances in the field of AChE and agrin neurobiology. View Full-Text
Keywords: acetylcholinesterase; in vitro innervation; human muscle; neuromuscular junction; co-cultures; agrin; apoptosis acetylcholinesterase; in vitro innervation; human muscle; neuromuscular junction; co-cultures; agrin; apoptosis
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Mis, K.; Grubic, Z.; Lorenzon, P.; Sciancalepore, M.; Mars, T.; Pirkmajer, S. In Vitro Innervation as an Experimental Model to Study the Expression and Functions of Acetylcholinesterase and Agrin in Human Skeletal Muscle. Molecules 2017, 22, 1418.

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