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 (ALS) linked superoxide dismutase 1 (SOD1) mutations develop a motoneuron disease 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 microtubular elements of the cytoskeleton of specific neuron populations including the spinal motoneurons. The aim of the present study was to measure changes in the relative Py-immunoreactivity per identified Choline-Acetyl-Transferase (ChAT)-immunoreactive motoneuron during the disease progression. The relative Py-immunoreactivity of identified spinal motoneurons was measured on double stained (Py and ChAT) motoneurons using a digital imaging system coupled to an inverse microscope. A significant decrease of Py-immunoreactivity was already noted in the pre-symptomatic stages of the disease even before the onset of massive motoneuron degeneration. It is concluded that the Py-antibody detects early intracellular abnormalities related to neurodegenerative changes in spinal motoneurons of transgenic SOD1-(G93A) mice.
Joosten
E A
EA
Laboratory of Experimental Neurology, Department of Neurology, Rudolf Magnus Institute for Neurosciences, Utrecht University, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. b.joosten@np.unimaas.nl
Van Westerlaak
M G
MG
Biesheuvel
C
C
Woodhams
P L
PL
Brook
G A
GA
Veldman
H
H
Bär
P R
PR
D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D003599:Cytoskeleton / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000276:immunology* / Q000473:pathology*; D009410:Nerve Degeneration / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
D000911:Antibodies, Monoclonal; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1