The neuromuscular junction microenvironment in extraocular and limb muscles

Abstract

Abstract Purpose To characterise the components of the neuromuscular junction (NMJ) in normal and pathological extraocular muscles (EOMs) and to assess the dynamics of progressive denervation. Methods Limb and EOM samples from 11 controls,8 ALS patients and from transgenic mice with SOD1 mutations (D90A, G93A) paralleling familiar ALS were processed for immunocytochemistry with antibodies against Schwann cell markers (S‐100, p75, GFAP), gangliosides GD1b and GQ1b/GT1a, neurotrophic factors (BDNF, GDNF, NT‐3, NT‐4) and their receptors, parvalbulmin, nestin, desmin and laminin chains. Results The NMJs of normal EOMs had a different cytoskeleton composition. Differences in the expression of gangliosides GD1b and GQ1b/GT1a, Schwann cell marker S‐100, agrin and nestin at the NMJs were noted in the human ALS EOMs. Parvalbumin was absent or scarce in EOM nerve trunks of ALS patients. The analysis of the time aspects of denervation in the animal models is ongoing. Conclusion The human EOMs in late stages of ALS and the EOMs of the transgenic mice show signs of denervation, although these muscles appear remarkably well preserved. High levels of parvalbumin, proposed to be protective for oculomotor neurons in ALS, are not apparent in advanced stages of the disease. The identification of similar endpoints in the EOMs of patients with D90A mutation and the ALS transgenic mice carrying the same mutation indicates that this is a useful model to study the temporal aspects of progressive denervation in the EOMs, to explore aspects of muscle‐nerve interplay that protect the EOMs in motoneuron disease and to gain further knowledge useful for the development of selective tools to modulate eye muscle function in the treatment of strabismus.