NEURONAL PATHOLOGY IN THE WOBBLER MOUSE-BRAIN REVEALED BY IN-VIVO PROTON MAGNETIC-RESONANCE SPECTROSCOPY AND IMMUNOCYTOCHEMISTRY

PROTON magnetic resonance spectroscopy (H-1-MRS) was used to measure t he in vivo signal of N-acetylaspartate (NAA), a putative neuronal mark er, in the brain of the mutant wobbler mouse, a model of motor neuron disease. The ratio of NAA to creatine-phosphocreatine, an internal sta ndard, was significantly lower in five affected wobbler mice (0.79 +/- 0.05; mean +/- s.d.) than in five unaffected littermates (0.98 +/- 0. 10, p = 0.006). Ubiquitin and phosphorylated heavy neurofilament immun oreactivities were increased in cortical neurons of affected animals. This is the first demonstration of cerebral neuronal pathology in the wobbler mouse, supporting its use as a model of amyotrophic lateral sc lerosis. In vivo H-1-MRS and correlative postmortem study of wobbler m ouse brain will allow temporal monitoring of neuronal degeneration and responsiveness to neuroprotective pharmacotherapies. NeuroReport 9: 3 041-3046 (C) 1998 Lippincott Williams & Wilkins.