Toxicity within superoxide dismutase-1 (SOD1)-associated familial amyotrophic lateral sclerosis (ALS) is non-cell autonomous with direct contribution from microglia. Microglia exhibit variable expression of neuroprotective and neurotoxic molecules throughout disease progression. The mechanisms regulating microglial phenotype within ALS are not well understood. This work presents a first study to examine the specific microglial phenotypic response in close association to motor neurons in a naturally occurring disease model of ALS, canine degenerative myelopathy (DM). Microglia closely associated with motor neurons were increased in all stages of DM progression, although only DM Late reached statistical significance. Furthermore, the number of arginase-1 expressing microglia per motor neuron were significantly increased in early stages of DM, whereas the number of inducible nitric oxide synthase (iNOS)-expressing microglia per motor neuron was indistinguishable from aged controls at all stages of disease. Fractalkine, a chemotactic molecule for microglia, was expressed in motor neurons, and the fractalkine receptor was specifically localized to microglia. However, we found no correlation between microglial response and lumbar spinal cord fractalkine levels. Taken together, these data suggest that arginase-1-expressing microglia are recruited to the motor neuron early in DM disease through a fractalkine-independent mechanism.

超氧化物歧化酶-1（SOD1）的毒性相关的家族性肌萎缩性侧索硬化症（ALS）是非细胞自主性的，由小胶质细胞直接贡献。小胶质细胞在整个疾病进展过程中表现出神经保护和神经毒性分子的可变表达。调节ALS内小胶质细胞表型的机制尚不清楚。这项工作提出了一项第一项研究，以检查在自然发生的ALS（犬类变性脊髓病）模型中，与运动神经元密切相关的特定小胶质细胞表型反应。尽管只有DM Late达到统计学意义，但与DM神经运动密切相关的小胶质细胞在DM进展的所有阶段均增加。此外，在DM的早期阶段，每个运动神经元表达精氨酸酶1的小胶质细胞的数量显着增加，而每个运动神经元的可诱导型一氧化氮合酶（iNOS）表达小胶质细胞的数量与老年对照在疾病的所有阶段都没有区别。Fractalkine是小胶质细胞的趋化分子，在运动神经元中表达，而fractalkine受体则专门定位于小胶质细胞。但是，我们发现小胶质细胞反应与腰椎脊髓中的fractalkine水平之间没有相关性。综上所述，这些数据表明，表达精氨酸酶1的小胶质细胞是通过不依赖fractalkine的机制在DM疾病早期募集到运动神经元的。但是，我们发现小胶质细胞反应与腰椎脊髓中的fractalkine水平之间没有相关性。综上所述，这些数据表明，表达精氨酸酶1的小胶质细胞是通过不依赖fractalkine的机制在DM疾病早期募集到运动神经元的。然而，我们发现小胶质细胞反应与腰椎脊髓分形碱水平之间没有相关性。综上所述，这些数据表明，表达精氨酸酶1的小胶质细胞是通过不依赖fractalkine的机制在DM疾病早期募集到运动神经元的。