Lin Tsen-Hsuan, Kim Joong Hee, Perez-Torres Carlos, Chiang Chia-Wen, Trinkaus Kathryn, Cross Anne H, Song Sheng-Kwei
Department of Physics, Washington University, St. Louis, MO 63130, USA.
Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Neuroimage. 2014 Oct 15;100:244-53. doi: 10.1016/j.neuroimage.2014.06.009. Epub 2014 Jun 14.
Optic neuritis is frequently the first symptom of multiple sclerosis (MS), an inflammatory demyelinating neurodegenerative disease. Impaired axonal transport has been considered as an early event of neurodegenerative diseases. However, few studies have assessed the integrity of axonal transport in MS or its animal models. We hypothesize that axonal transport impairment occurs at the onset of optic neuritis in experimental autoimmune encephalomyelitis (EAE) mice. In this study, we employed manganese-enhanced MRI (MEMRI) to assess axonal transport in optic nerves in EAE mice at the onset of optic neuritis. Axonal transport was assessed as (a) optic nerve Mn(2+) accumulation rate (in % signal change/h) by measuring the rate of increased total optic nerve signal enhancement, and (b) Mn(2+) transport rate (in mm/h) by measuring the rate of change in optic nerve length enhanced by Mn(2+). Compared to sham-treated healthy mice, Mn(2+) accumulation rate was significantly decreased by 19% and 38% for EAE mice with moderate and severe optic neuritis, respectively. The axonal transport rate of Mn(2+) was significantly decreased by 43% and 65% for EAE mice with moderate and severe optic neuritis, respectively. The degree of axonal transport deficit correlated with the extent of impaired visual function and diminished microtubule-associated tubulins, as well as the severity of inflammation, demyelination, and axonal injury at the onset of optic neuritis.
视神经炎通常是多发性硬化症（MS）的首发症状，多发性硬化症是一种炎症性脱髓鞘神经退行性疾病。轴突运输受损被认为是神经退行性疾病的早期事件。然而，很少有研究评估多发性硬化症或其动物模型中轴突运输的完整性。我们假设在实验性自身免疫性脑脊髓炎（EAE）小鼠视神经炎发作时会出现轴突运输受损。在本研究中，我们采用锰增强磁共振成像（MEMRI）来评估EAE小鼠视神经炎发作时视神经中的轴突运输。通过测量视神经总信号增强率评估轴突运输为（a）视神经锰（2+）积累率（以%信号变化/小时计），以及通过测量锰（2+）增强的视神经长度变化率评估（b）锰（2+）运输率（以毫米/小时计）。与假手术处理的健康小鼠相比，中度和重度视神经炎的EAE小鼠的锰（2+）积累率分别显著降低了19%和38%。中度和重度视神经炎的EAE小鼠的锰（2+）轴突运输率分别显著降低了43%和65%。轴突运输缺陷程度与视神经炎发作时视觉功能受损程度、微管相关微管蛋白减少以及炎症、脱髓鞘和轴突损伤的严重程度相关。
