Cellular changes in motoneurons in a transgenic mouse model for amyotrophic lateral sclerosis as revealed by monoclonal antibody Py

Transgenic mice (G93A) carrying the human amyotrophic lateral sclerosis (AL S) linked superoxide dismutase I (SOD1) mutations develop a motoneuron dise ase resembling human ALS. The affected motoneurons are characterized by the presence of cellular alterations. The antigen recognized by the monoclonal antibody Py is suggested to be associated with the neurofilamentous and mi crotubular elements of the cytoskeleton of specific neuron populations incl uding the spinal motoneurons. The aim of the present study was to measure c hanges in the relative Py-immunoreactivity per identified Choline-Acetyl-Tr ansferase (ChAT)-immunoreactive motoneuron during the disease progression. The relative Py-immunoreactivity of identified spinal motoneurons was measu red on double stained (Py and ChAT) motoneurons using a digital imaging sys tem coupled to an inverse microscope. A significant decrease of Py-immunore activity was already noted in the pre-symptomatic stages of the disease eve n before the onset of massive motoneuron degeneration. It is concluded that the Py-antibody detects early intracellular abnormalities related to neuro degenerative changes in spinal motoneurons of transgenic SOD1-(G93A) mice. (C) 2001 Elsevier Science B.V. All rights reserved.