Progressive dopaminergic neurodegeneration of substantia nigra in the zitter mutant rat

Kazuhiko Nakadate*, Takahiro Noda, Shin Ichi Sakakibara, Kenzo Kumamoto, Tadao Matsuura, Jeffery N. Joyce, Shuichi Ueda


研究成果: Article査読

20 被引用数 (Scopus)


Zitter mutant rats exhibit abnormal metabolism of superoxide species and demonstrate progressive degeneration of dopamine (DA) neurons in the substantia nigra (SN). Furthermore, long-term intake of vitamin E, an effective free radical scavenger, prevents the loss of DA neurons caused by free radicals. However, it is unclear how this degeneration progresses. In this study, we ultrastructurally examined cell death in the zitter mutant rat SN. Conventional electron-microscopic examination revealed two different types of neurons in the SN pars compacta. In zitter mutant rats, although the first type (clear neurons) exhibited no obvious ultrastructural changes with aging, the second type (dark neurons) demonstrated age-related damage from 2 months. Immunoelectron-microscopic analysis clarified that the second-type neurons were dopaminergic neurons. In the dopaminergic neuronal somata, many lipofuscin granules and abnormal endoplasmic reticula were observed from 2 months of age, and these dopaminergic neurons showed progressive degeneration with age. Moreover, in zitter mutant rats, abnormally enlarged myelinated axons with dense bodies and splitting myelin with dense material were observed in the SN at 2, 4, and 12 months, and oligodendrocytes with numerous lipofuscin, multivesicular bodies, multilamellar bodies, and dense bodies were frequently observed at 4 and 12 months. These findings clarified that dopaminergic neurons in zitter mutant rats had degenerated with age, and that myelinated axons also exhibited age-related injury. Moreover, ubiquitin-immunohistochemical analysis indicated that the accumulation of products of the endosomal-lysosomal system may be involved in this degeneration.

ジャーナルActa Neuropathologica
出版ステータスPublished - 2006 7月

ASJC Scopus subject areas

  • 病理学および法医学
  • 臨床神経学
  • 細胞および分子神経科学


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