Presymptomatic motor neuron loss and reactive astrocytosis in the sod1 mouse model of amyotrophic lateral sclerosis

In familial amyotrophic lateral sclerosis (fALS), there is a need to establ ish more precisely the progression of the disease, particularly whether the re is gradual presymptomatic neuronal loss or an abrupt loss coinciding wit h the symptomatic stage. To elucidate this, we investigated the progression of motor neuron loss through morphological techniques, reactive astrocytos is, and expression of ubiquitin and neurofilament proteins, by immunohistoc hemistry, in SOD1 G93A mice with a protracted disease course and control mi ce. Loss of motor neurons in SOD1 G93A mice followed a biphasic progression , with an initial loss at 126 days of age, followed by a gradual loss from onset of symptoms through to end-stage disease. Reactive astrocytosis was f irst observed at 70 days of age and showed a gradual increase through to en d-stage disease. This suggests that there is a need for early detection of fALS cases, and potential therapeutic treatments may be more beneficial if administered at an early stage. (C) 2001 John Wiley & Sons, Inc.