Abstract
Purpose: :
To study the distribution of several neurotrophins and their receptors in extraocular and limb muscles from terminal patients with ALS and in normal controls.
Methods: :
EOM and limb samples obtained at autopsy from 7 ALS cases and from 4 elderly controls were processed for immunocytochemistry with monoclonal antibodies against NGF, BDNF, NT-3, NT-4, TrkA, TrkB, TrkC. Neuromuscular junctions (NMJs) were identified with alpha-bungarotoxin.
Results: :
NGF, NT-3 and -TrkA showed higher staining intensity in normal EOMs than in limb muscles.The level of NGF was increased to some extent in fibers in ALS limb muscles, especially in small sized fibers. High levels of NGF were found at NMJs in both ALS limb and EOMs, but not in controls.There was no significant change in immunoreactivity with anti-BDNF in ALS EOMs compared to controls.Immunoreactivity with NT-3 and NT-4 antibodies, which normally selectively stain slow and fast fibers respectively, was substantially reduced in muscle fibers in EOMs with ALS, whereas there was no significant change in the reactivity to these antibodies in intramuscular nerves in ALS. NT-3 was completely absent in atrophic slow fibers and weak in the remaining slow fibers in ALS limb muscles.TrkA was present in EOM fibers in ALS but weaker than in controls. TrkB stained EOM slow fibers weakly in ALS and strongly in controls. Intramuscular nerves were moderately stained with TrkC in ALS EOMs and the muscle fibers were unstained in ALS and control EOMs.
Conclusions: :
The neurotrophins and their receptors are essential for development, maintenance, function and regeneration of skeletal muscles. EOMs differed from limb muscles by possessing higher levels of NT-3, NGF and TrkA. We showed significant alterations in neurotrophins (NT-3, NT-4 and NGF) and the receptor TrkB in EOMs of ALS patients. These differences in profile may be protective in ALS, as the EOMs are significantly less affected than limb muscles in this disease.
Keywords: pathology: human • extraocular muscles: structure • extracellular matrix