title: 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.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. Email: auchidak@mail.ecc.u-tokyo.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.forename: O
authors.initials: O
authors.lastname: Yamato
authors.forename: M
authors.initials: M
authors.lastname: Inaba
authors.forename: M M
authors.initials: MM
authors.lastname: Uddin
authors.forename: H
authors.initials: H
authors.lastname: Nakayama
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000870:Anterior Horn Cells / Q000473:pathology*; D004283:Dog Diseases / Q000378:metabolism* / Q000473:pathology*; D004285:Dogs; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005455:Fluorescent Antibody Technique / Q000662:veterinary; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006652:Histological Techniques / Q000662:veterinary; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000662:veterinary; D009410:Nerve Degeneration / Q000473:pathology / Q000662:veterinary*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D013569:Synapses / Q000473:pathology
chemical_list: D027322:Amino Acid Transport System X-AG; D027342:Excitatory Amino Acid Transporter 2; D005974:Glutamate-Ammonia Ligase
keywords: amyotrophic lateral sclerosis; dog; excitatory amino acid transporter; excitotoxicity; immunohistochemistry; neurodegenerative disease; spinal cord