Normal and pathological neuro-muscular development in man and animal models

The differentiation of muscle cells during development and pathologically-induced alterations results in the variation of some important indexes; among these are the isoforms of myosin, the acetylcholine receptor subunits and the levels and molecular forms of acetylcholinesterase (AChE). We have studied the variations in AChE activity and molecular forms in different experimental conditions: 1) Denervation and reinnervation process in rat muscles. 2) Maturation of myogenic mouse cells (early myoblast, late myoblast, and satellite cells). 3) Muscular distrophy in genetically dystrophic mice. 4) Non-dystrophic child myopathies. The results of our experiments indicate that: 1) The most complex asymmetric molecular form (A12) appears to represent a significant index of the establishment of synaptic contacts. 2) The study of the levels of A12 form in the cells and their culture medium in different experimental conditions supports the hypothesis that the three different myogenic cells are endowed with different maturation programs. 3) The AChE molecular forms pattern is altered in dystrophic mouse muscles, showing a selective and marked reduction of one particular form (the tetrameric one inserted in the area of the membrane probably near the acetylcholine receptor). 4) The complete disappearance of high and medium molecular forms of AChE is a characteristic of 60% of "myopathic non-dystrophic" patients. This last observation enables the differentiation of two distinct groups within a population of subjects affected by pathologies of a hitherto indistinctly defined aetiology.