Altered glucose catabolism in the presynaptic and perisynaptic compartments of SOD1G93A mouse spinal cord and motor cortex indicates that mitochondria are the site of bioenergetic imbalance in ALS.

摘要: Amyotrophic lateral sclerosis is an adult-onset neurodegenerative disease that develops because of motor neuron death. Several mechanisms occur supporting neurodegeneration, including mitochondrial dysfunction. Recently, we demonstrated the synaptosomes from spinal cord SOD1G93A mice, in vitro model presynapses, displayed impaired metabolism at early pre-symptomatic stages disease, whereas perisynaptic astrocyte particles, or gliosomes, were characterized by mild energy impairment only symptomatic stages. This work aimed to understand whether a consequence upstream metabolic damage. We analyzed critical pathways involved glucose catabolism presynaptic and compartments. Spinal cortex mice high activity hexokinase phosphofructokinase, key glycolysis enzymes, citrate synthase malate dehydrogenase, Krebs cycle but did not display lactate dehydrogenase activity, enzyme fermentation. enhancement was evident Conversely, increase fermentation observed gliosomes although disease. The cited enzymatic activities enhanced homogenates, paralleling time-course effect gliosomes. modifications might be considered attempt restore altered energetic balance indicate mitochondria represent ultimate site bioenergetic impairment.