Differential involvement of vesicular and glial glutamate transporters around spinal α-motoneurons in the pathogenesis of SOD1G93A mouse model of amyotrophic lateral sclerosis

Neuroscience
Tomohiro OhgomoriShozo Jinno

Abstract

From a view point of the glutamate excitotoxicity theory, several studies have suggested that abnormal glutamate homeostasis via dysfunction of glial glutamate transporter-1 (GLT-1) may underlie neurodegeneration in amyotrophic lateral sclerosis (ALS). However, the detailed role of GLT-1 in the pathogenies of ALS remains controversial. To assess this issue, here we elucidated structural alterations associated with dysregulation of glutamate homeostasis using SOD1G93A mice, a genetic model of familial ALS. We first examined the viability of α-motoneurons in the lumbar spinal cord of SOD1G93A mice. Measurement of the soma size and density indicated that α-motoneurons might be intact at 9weeks of age (presymptomatic stage), then soma shrinkage began at 15weeks of age (progressive stage), and finally neuronal density declined at 21weeks of age (end stage). Next, we carried out the line profile analysis, and found that the coverage of α-motoneurons by GLT-1-positive (GLT-1+) astrocytic processes was decreased only at 21weeks of age, while the reduction of coverage of α-motoneurons by synaptophysin-positive (SYP+) presynaptic terminals began at 15weeks of age. Interestingly, the coverage of α-motoneurons by VGluT2+ presynaptic termin...Continue Reading

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