Harandi Vahid M, Gaied Aida R N, Brännström Thomas, Pedrosa Domellöf Fatima, Liu Jing-Xia
Department of Integrative Medical Biology, Section for Anatomy, Umeå University, Umeå, Sweden 2Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden.
Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden.
Invest Ophthalmol Vis Sci. 2016 Dec 1;57(15):6831-6842. doi: 10.1167/iovs.16-20074.
To investigate the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the distribution of neurotrophic factors (NTFs) and their receptors in EOMs and limb muscles from ALS transgenic mice.
Muscle samples collected from transgenic mice overexpressing human superoxide dismutase type 1 mutations (SOD1G93A, the most widely used mouse model of ALS) at 50 and 150 days as well as age-matched controls were analyzed with immunohistochemistry using antibodies against brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4), glial cell line-derived neurotrophic factor (GDNF), and the neurotrophin receptors p75NTR, tyrosine kinase (Trk) receptor TrkB and TrkC, and GDNF family receptor alpha-1 (GFRα-1).
There was an intrinsic difference in NTF expression between EOMs and limb muscles in control mice: EOMs presented significantly lower number of neuromuscular junctions (NMJs) labeled for BDNF and NT-4 at 50 days, and for BDNF and GDNF at 150 days, compared with the control limb muscles of corresponding age. In ALS transgenic mice at 150 days, NTF expression in limb muscles was significantly changed but not in EOMs: the limb muscles presented a significant decline in the number of NMJs labeled for BDNF, NT-4, GDNF, p75NTR, TrkB, and TrkC, which was not observed in EOMs.
The significant differences in expression of NTFs on NMJs between EOMs and limb muscles in both control and ALS transgenic mice suggest that NTF may be involved in the pathogenesis of ALS and the resistance of EOMs to the disease.
通过检测神经营养因子（NTFs）及其受体在肌萎缩侧索硬化症（ALS）转基因小鼠眼外肌（EOMs）和肢体肌肉中的分布，研究ALS对眼外肌的影响。
收集过表达人超氧化物歧化酶1突变体（SOD1G93A，最广泛使用的ALS小鼠模型）的转基因小鼠在50天和150天时的肌肉样本，以及年龄匹配的对照小鼠的肌肉样本，使用针对脑源性神经营养因子（BDNF）、神经营养因子-3（NT-3）、神经营养因子-4/5（NT-4）、胶质细胞源性神经营养因子（GDNF）以及神经营养因子受体p75NTR、酪氨酸激酶（Trk）受体TrkB和TrkC、GDNF家族受体α-1（GFRα-1）的抗体进行免疫组织化学分析。
对照小鼠中，EOMs和肢体肌肉在NTF表达上存在内在差异：与相应年龄的对照肢体肌肉相比，EOMs在50天时标记BDNF和NT-4的神经肌肉接头（NMJs）数量显著减少，在150天时标记BDNF和GDNF的神经肌肉接头数量显著减少。在150天龄的ALS转基因小鼠中，肢体肌肉中的NTF表达显著改变，而EOMs中未改变：肢体肌肉中标记BDNF、NT-4、GDNF、p75NTR、TrkB和TrkC的NMJs数量显著下降，而EOMs中未观察到这种情况。
对照小鼠和ALS转基因小鼠的EOMs与肢体肌肉中NMJs上NTF表达的显著差异表明，NTF可能参与ALS的发病机制以及EOMs对该疾病的抗性。
