Expression of Autophagy-Related Proteins in the Spinal Cord of Pembroke Welsh Corgi Dogs With Canine Degenerative Myelopathy.
Canine degenerative myelopathy (DM) is a progressive neurodegenerative disease frequently found in Pembroke Welsh Corgi (PWC) dogs, and it has clinical and pathologic similarities to human amyotrophic lateral sclerosis. Autophagy is a major intracellular protein degradation system. Abnormalities of autophagy--resulting in cell death through mechanisms called type II programmed cell death--have recently been reported to occur in various neurodegenerative diseases, including amyotrophic lateral sclerosis. Thus, the distribution and expression levels of proteins involved in autophagy were examined in the spinal cords of 8 PWC dogs suffering from DM with superoxide dismutase mutation, 5 non-DM PWC dogs, and 6 Beagle dogs without neurologic signs. There was no significant difference in the ratio of neurons with microtubule-associated protein light chain 3 (LC3)-positive somata relative to those that were LC3 negative among the 3 groups, whereas the number of LC3-positive neurites was significantly increased in DM dogs. Punctate LC3 immunoreactivity did not colocalize with a lysosome marker, LAMP2 (lysosome-associated membrane protein 2). NBR1 (neighbor of BRCA gene 1) was localized mostly in reactive astrocytes, whereas there were p62 (p62/A170/SQSTM1)-positive foci in the neuropil of the spinal cord of DM dogs. Western blotting revealed in DM dogs the decreased expression of Beclin1 and Atg16 L, which are molecules involved in formation of the isolation membrane. These findings suggest that altered autophagosome degradation may result in LC3 and p62 accumulation in the DM spinal cord, whereas the early stage of membrane formation is likely to be downregulated.
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
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M
Ogawa
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan auchidak@mail.ecc.u-tokyo.ac.jp.
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K
Uchida
Department of Veterinary Medicine, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
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O
Yamato
Department of Veterinary Medicine, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
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K
Mizukami
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
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JK
Chambers
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
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Nakayama
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D004283:Dog Diseases / Q000378:metabolism / Q000473:pathology*; D004285:Dogs; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013118:Spinal Cord Diseases / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
D008869:Microtubule-Associated Proteins; D013482:Superoxide Dismutase
amyotrophic lateral sclerosis; apoptosis; autophagy; canine degenerative myelopathy; dog; neurodegenerative disease