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

Tomohiro Ohgomori, Ryo Yamasaki, Hideyuki Takeuchi, Kenji Kadomatsu, Jun ichi Kira, Shozo Jinno

研究成果: ジャーナルへの寄稿記事

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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 9 weeks of age (presymptomatic stage), then soma shrinkage began at 15 weeks of age (progressive stage), and finally neuronal density declined at 21 weeks 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 21 weeks of age, while the reduction of coverage of α-motoneurons by synaptophysin-positive (SYP+) presynaptic terminals began at 15 weeks of age. Interestingly, the coverage of α-motoneurons by VGluT2+ presynaptic terminals was transiently increased at 9 weeks of age, and then gradually decreased towards 21 weeks of age. On the other hand, there were no time-dependent alterations in the coverage of α-motoneurons by GABAergic presynaptic terminals. These findings suggest that VGluT2 and GLT-1 may be differentially involved in the pathogenesis of ALS via abnormal glutamate homeostasis at the presymptomatic stage and end stage of disease, respectively.

元の言語英語
ページ(範囲)114-124
ページ数11
ジャーナルNeuroscience
356
DOI
出版物ステータス出版済み - 7 25 2017

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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