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Neurobiol Dis. 2006 Jun;22(3):599-610. Epub 2006 Apr 17.

Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal cord pathology in the G93A SOD1 mouse model of ALS.

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Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 E. 68th Street, A-502, New York, NY 10021, USA.


Multiple cell death pathways are implicated in the etiology of amyotrophic lateral sclerosis (ALS), but the cause of the characteristic motor neuron degeneration remains unknown. To determine whether CNS metabolic defects are critical for ALS pathogenesis, we examined the temporal evolution of energetic defects in the G93A SOD1 mouse model of familial ALS. [14C]-2-deoxyglucose in vivo autoradiography in G93A mice showed that glucose utilization is impaired in components of the corticospinal and bulbospinal motor tracts prior to either pathologic or bioenergetic changes in the spinal cord. This was accompanied by significant depletions in cortical ATP content in presymptomatic mice, which was partially ameliorated by creatine administration. Findings suggest that bioenergetic defects are involved in the initial stages of mSOD1-induced toxicity in G93A mice and imply that the selective dysfunction and degeneration of spinal cord motor neurons in this model may be secondary to dysfunction within cerebral motor pathways.

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