Expression of Autophagy-Related Proteins in the Spinal Cord of Pembroke Welsh Corgi Dogs With Canine Degenerative Myelopathy. (November 2015)

• Record Type: Journal Article
• Authors: Ogawa, M.; Uchida, K.; Yamato, O.; Mizukami, K.; Chambers, J.K.; Nakayama, H.
• Is Part Of: Veterinary pathology. Volume 52:Number 6(2015:Nov.)
• Page Start: 1099
• Page End: 1107
• Publication Date: 2015-11
• Subjects: amyotrophic lateral sclerosis -- dog -- autophagy -- apoptosis -- neurodegenerative disease -- canine degenerative myelopathy; Veterinary pathology -- Periodicals; Pathology, Veterinary -- Periodicals; 636.089607
• DOI: 10.1177/0300985815570070
• Languages: English
• ISSNs: 0300-9858

Abstract

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.