Neuronal loss and decreased GLT-1 expression observed in the spinal cord of Pembroke Welsh Corgi dogs with canine degenerative myelopathy.

Abstract

Canine degenerative myelopathy (DM) is a progressive neurodegenerative disease that is frequently found in Pembroke Welsh Corgi (PWC) dogs. Canine DM is potentially a spontaneous animal model for human amyotrophic lateral sclerosis (ALS) because of similar lesions and the involvement of superoxide dismutase 1 (SOD1) mutation. However, the ventral horn lesion in DM has not been characterized in detail. Glutamate excitotoxicity due to deficiency of the glutamine-glutamate cycle has been implicated in neuron death in ALS. Thus, we examined 5 PWC dogs with an SOD1 mutation that were affected by DM, 5 non-DM PWC dogs, and 5 Beagle dogs without neurologic signs to assess the neuronal changes and the expression levels of 2 glial excitatory amino acid transporters (glutamate transporter 1 [GLT-1] and glutamate/aspartate transporter [GLAST]). The number of neurons in the spinal ventral horns of the DM dogs was significantly decreased, whereas no change was found in the cell size. Chromatolysis, lipofuscin-laden neurons, and marked synapse loss were also observed. GLT-1 expression was strikingly decreased in DM dogs, whereas GLAST expression showed no significant change. The results indicate that excitotoxicity related to the reduced expression of GLT-1, but not GLAST, may be involved in neuron loss in DM, as in human ALS, whereas intraneuronal events may differ between the 2 diseases.

• Authors: M Ogawa, K Uchida, O Yamato, M Inaba, M M Uddin, H Nakayama
• Journal: Veterinary pathology (Vet Pathol) Vol. 51 Issue 3 Pg. 591-602 (May 2014) ISSN: 1544-2217 [Electronic] United States
• PMID: 23839236 (Publication Type: Journal Article)

Chemical References

• Amino Acid Transport System X-AG
• Excitatory Amino Acid Transporter 2
• Glutamate-Ammonia Ligase

Topics

• Amino Acid Transport System X-AG (metabolism)
• Analysis of Variance
• Animals
• Anterior Horn Cells (pathology)
• Dog Diseases (metabolism, pathology)
• Dogs
• Excitatory Amino Acid Transporter 2 (metabolism)
• Fluorescent Antibody Technique (veterinary)
• Glutamate-Ammonia Ligase (metabolism)
• Histological Techniques (veterinary)
• Image Processing, Computer-Assisted
• Immunohistochemistry (veterinary)
• Nerve Degeneration (pathology, veterinary)
• Neurodegenerative Diseases (metabolism, pathology, veterinary)
• Synapses (pathology)