Immunohistochemical and morphometrical studies on myelin breakdown in the demyelination (dmy) mutant rat.
The demyelination (dmy) rat is a unique mutant exhibiting severe myelin breakdown in the central nervous system (CNS). In this study, we conducted immunohistochemical and morphometrical investigations in the dmy rat. From around 6 weeks of age, the affected rats developed ataxia especially in the hindlimbs. Afterwards, ataxia worsened rapidly, resulting in complete paralysis of the hindlimbs and recumbency. Histopathology at 7 to 10 weeks of age revealed myelin destruction throughout the white matter of the CNS in the dmy rats. The most severely affected lesions were distributed in the corpus callosum, capsula interna, striatum, subcortical white matter, cerebellar peduncle, and ventral and lateral parts of the spinal cord. Immunohistochemistry demonstrated prominent astrogliosis and many ED-1 positive macrophages in the myelin-destructed areas. Until the 4th week, no significant differences in myelin thickness and fiber diameter were found between dmy and control rats. However, from 5 weeks of age, myelin thickness of residual myelinated fibers in dmy rats became significantly less than that in controls. These data indicated that the dmy phenotype shows a prolonged period of myelin destruction, suggesting that dmy mutation affects the adequate maintenance of myelin.
Kuwamura
Mitsuru
M
Laboratory of Veterinary Pathology, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan. kuwamura@vet.osakafu-u.ac.jp
Kanehara
Toshiko
T
Tokuda
Satoko
S
Kumagai
Daijiro
D
Yamate
Jyoji
J
Kotani
Takao
T
Nakane
Yoshifumi
Y
Kuramoto
Takashi
T
Serikawa
Tadao
T
D000367:Age Factors; D000818:Animals; D001369:Axons / Q000473:pathology; D020934:Ciliary Neurotrophic Factor; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006652:Histological Techniques / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
D020934:Ciliary Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; C118937:axokine