氏名

西沢 富江

学位の種類

博士（体育学）

学位記番号第２号

学位授与の要件 学位規則第４条第１項該当
学位授与年月日 平成 19 年 3 月 23 日
学位論文題目

Plasticity of neuromuscular junction architectures in rat slow and fast muscle
fibers following temporary denervation and reinnervation processes

論文審査委員

主査 教授 竹倉 宏明
副査 教授 浜岡 隆文
副査 教授 齋藤 和人

論

文 概 要

The neuromuscular junctions (NMJs) in skeletal muscle fibers are functionally distinct
compartments of the subsarcolemmal and extracellular matrix domains that contain variantsof the sub- and trans-sarcolemmal components and of the extracellular matrix. The NMJ is the
only synaptic link between a motor neuron and the muscle fiber it innervates. It is a chemical
synapse that is anatomically and functionally differentiated for the transmission of signals
from the motor nerve terminal to a circumscribed postsynaptic region on the muscle fiber. TheNMJs of mammalian skeletal muscle have several components: (1) a Schwann cell process thatforms a cap above the portion of the nerve terminal that does not face the postsynaptic region;(2) a nerve terminal, which contains the neurotransmitter acetylcholine; (3) a synaptic space
lined with basement membrane; (4) a postsynaptic membrane containing acetylcholine
receptors and acetylcholine esterase; and (5) junctional sarcoplasm, which provides structuraland metabolic support for the postsynaptic region.
We evaluated the effects of brief, temporary denervation caused by ischiadic
nerve-freezing on the processes of degeneration and regeneration of ultrastructural features inneuromuscular junction (NMJ) architecture in different types of rat skeletal muscle fibers.
Nerve terminal (NT) area was decreased significantly 12 hours after nerve freezing in both
fast-twitch (FT) and slow-twitch (ST) fibers. One day after nerve freezing, some terminal axons
were absent; decrease in NT area was remarkable in ST fibers, and there was retraction of
Schwann cells and perineural epithelial cells. Fiber type-specific differences were observed inpattern of decrease in NT area between 24 hours and 7 days after nerve freezing (there wassignificantly more decrease in FT fibers). The primary synaptic cleft became shallow, and thesecondary junctional folds shorter and wider, but the basement lamina filling the subneuralapparatus was unaltered. The number of secondary junctional folds decreased gradually
between 6 hours and 14 days after nerve freezing in both types of fiber. In control muscle fibers,
synaptic vesicle density (SVD) per terminal area was significantly higher in FT fibers. SVD
densities decreased following nerve freezing-induced destruction of NMJs, and were minimal 3
days in FT fibers or 7 days ST fibers after nerve freezing. At 3 weeks, regeneration of both FTand ST fibers was well advanced, and all parameters had recovered to control values in FT
fibers 28 days after nerve freezing. The effects of structural degeneration of NMJs were lesspronounced in FT fibers, and regeneration tended to be earlier in FT than in ST fibers.
These findings indicate that maintenance of the cup-shaped primary folds is dependent
upon neurotrophism, while secondary junctional fold structure is not. If muscular activity were
the only trophic influence on skeletal muscle fibers, then denervation would affect NMJs in allfiber types to the same extent, and any difference in rate of degeneration between the two typesof muscle fibers would be due to factors intrinsic to them. If, however, neurotrophic factors(postulated to be one component of the dense-core vesicles in the nerve terminals) are partially
responsible for maintenance of muscle fiber structures, then differences in rates ofdegeneration and regeneration of NMJs in different types of muscle fibers could result indifferential withdrawal of neurotrophic substances. Severe degradation of the ultrastructuralfeatures in NMJs occurred due to temporary denervation during muscle fiber degeneration-1-processes, and these structural changes were all reversible and fiber type-specific.
論文 審 査の 要 旨

学位論文の「Plasticity of neuromuscular junction architectures in rat slow and fast muscle fibers
following temporary denervation and reinnervation processes」は、2006 年 11 月発行の J. Muscle Res. CellMotil.の第 27 巻、8 号に原著論文として掲載された（607-615）。研究内容の主体は、骨格筋細胞における神経筋接合部の形態変化を機能的特性と関連させ、組織化学的手法により検討したものであり、最新のバイオイメージング技術を駆使して実施した極めて独創性の高い研究成果であった。骨格筋細胞のタイプ移行に関係する運動神経細胞の支配様式は、筋線維タイプ別に異なることが報告されているが、神経筋接合部の形態的特性も大きく異なることに加え、生理的・非生理的刺激に応答して比較的容易にその形態的特徴を変化させることによって機能的特性の変化を引き起こしていると推察された。
学位論文審査委員会では合議によって、本研究内容に加えて関連する研究成果を総合的に判断し、本論文は博士の学位を授与するに十分な研究成果を含む内容であると判定した。

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