NEUROFILAMENT DISTRIBUTION IS ALTERED IN THE MND (MOTOR-NEURON DEGENERATION) MOUSE

Motor neuron degeneration (Mnd) is a genetic neurodegenerative disease of the mouse that is characterized by a progressive increase in motor dysfunction, moving from hind to fore limbs, leading to paralysis. An immunocytochemical analysis of the neurofilament distribution in spinal motor neurons in Mnd mice from all stages of the disease, including the presymptomatic, was performed using antibodies to different neurofilament subunits with different degrees of phosphorylation. Perikarya that stained with antibodies to phosphorylated neurofilaments were present in Mnd and control spinal cords, but the number of stained perikarya in Mnd was not significantly different from controls. There was a marked redistribution of neurofilaments within the cytoplasm of some motor neurons in Mnd cords. In Mnd but not controls, the immunoreaction product appeared marginated, leaving areas in the cytoplasm absent of immunostaining. These areas were observed in all stages of the disease, but less predictably in presymptomatics. Both the size of the areas and the number of motoneurons containing these areas appeared to increase with the severity of the disease. The number of anterior horn neurons in the hind limb region of lamina IX in spinal segment L4 of Mnd was lower than in controls, suggesting there is a loss of neurons in Mnd.