Neuronal Loss and Decreased GLT-1 Expression Observed in the Spinal Cord of Pembroke Welsh Corgi Dogs With Canine Degenerative Myelopathy
Neuronal Loss and Decreased GLT-1 Expression Observed in the Spinal Cord of Pembroke Welsh Corgi Dogs With Canine Degenerative Myelopathy
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DOI：
10.1177/0300985813495899
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发表时间：
2014-05-01
影响因子：
2.4
通讯作者：
Nakayama, H.
中科院分区：
文献类型：
--
作者：
Ogawa, M.;Uchida, K.;Nakayama, H.
犬退行性脊髓病（DM）是一种进行性神经退行性疾病，常见于彭布罗克威尔士柯基犬（PWC）。犬DM是潜在的人类肌萎缩侧索硬化症（ALS）的自发动物模型，因为类似的病变和超氧化物歧化酶1（SOD 1）突变的参与。然而，糖尿病的腹角病变还没有详细的特点。由于谷氨酰胺-谷氨酸循环的缺陷引起的谷氨酸兴奋性毒性与ALS中的神经元死亡有关。因此，我们检查了5只受DM影响的SOD 1突变PWC犬、5只非DM PWC犬和5只无神经系统体征的比格犬，以评估神经元变化和2种神经胶质兴奋性氨基酸转运蛋白（谷氨酸转运蛋白1 [GLT-1]和谷氨酸/天冬氨酸转运蛋白[GLAST]）的表达水平。糖尿病犬脊髓腹角神经元数量明显减少，而细胞大小无明显变化。还观察到染色质溶解、充满脂褐素的神经元和显著的突触丢失。GLT-1表达在DM犬中显著降低，而GLAST表达无显著变化。结果表明，兴奋性毒性相关的GLT-1的表达减少，但不GLAST，可能参与神经元损失的DM，在人类ALS，而神经元内的事件可能不同的2种疾病。
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 intra-neuronal events may differ between the 2 diseases.