title: Early detachment of neuromuscular junction proteins in ALS mice with SODG93A mutation.
abstract: The transgenic animals with mutant copper/zinc superoxide dismutase (SOD1) DNA develop paralytic motor neuron disease resembling human amyotrophic lateral sclerosis (ALS) patients and are commonly used as models for ALS. In the transgenic (Tg) mice with the G93A mutation of the human SOD1 gene SOD1(G93A) mice), the loss of ventral root axons and the synapses between the muscles and the motor neurons suggested that the motor neuron degeneration might proceed in a dying-back degeneration pattern. To reveal the relationship between axonal degeneration and the progression of the muscle atrophy in the SOD1(G93A) mice, we investigated the status of the neuromuscular junction along the disease progression. As a presynaptic or postsynaptic marker of neuromuscular junction (NMJ), anti-synaptic vesicle protein 2 (anti-SV2) antibody and α-bungarotoxin (α-BuTX) were chosen in this study and, as a marker of synaptic cleft, anti-agrin antibody was chosen in this study. In the immunohistochemistry of α-BuTX and anti-SV2 antibody, the percentages of double positive NMJs among α-BuTX single positive were decreased in Tg mice through time from ten weeks. The number of postsynaptic acethylcholine receptor (AChR) clusters did not decrease in Tg mice even at the end stage. Immunohistochemistry of α-BuTX and anti-agrin antibody revealed that the increase of immunopositive area of anti-agrin antibody around the muscle fiber in Tg mice from ten weeks of age. In this study, we revealed that the detachment of nerve terminals started at ten weeks in Tg mice. The levels of AChR did not change throughout 5-20 weeks of age in both groups of mice, and AChR remains clustering at NMJs, suggesting that the muscle abnormality is the result of detachment of nerve terminals.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan;
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Manabe
authors.forename: Makiko
authors.initials: M
authors.lastname: Nagai
authors.forename: Isao
authors.initials: I
authors.lastname: Nagano
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohta
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Murakami
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takehisa
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Kamiya
authors.forename: Koji
authors.initials: K
authors.lastname: Abe