Li Hong-Ying, Hong Xi, Huang Mi, So Kwok-Fai
Department of Anatomy, School of Medicine; Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, Guangdong Province, China.
Department of Anatomy, School of Medicine, Jinan University, Guangzhou, Guangdong Province, China.
Neural Regen Res. 2019 Apr;14(4):728-734. doi: 10.4103/1673-5374.247481.
Running is believed to be beneficial for human health. Many studies have focused on the neuroprotective effects of voluntary running on animal models. There were both primary and secondary degeneration in neurodegenerative diseases, including glaucoma. However, whether running can delay primary or secondary degeneration or both of them was not clear. Partial optic nerve transection model is a valuable glaucoma model for studying both primary and secondary degeneration because it can separate primary (mainly in the superior retina) from secondary (mainly in the inferior retina) degeneration. Therefore, we compared the survival of retinal ganglion cells between Sprague-Dawley rat runners and non-runners both in the superior and inferior retinas. Excitotoxicity, oxidative stress, and apoptosis are involved in the degeneration of retinal ganglion cells in glaucoma. So we also used western immunoblotting to compare the expression of some proteins involved in apoptosis (phospho-c-Jun N-terminal kinases, p-JNKs), oxidative stress (manganese superoxide dismutase, MnSOD) and excitotoxicity (glutamine synthetase) between runners and non-runners after partial optic nerve transection. Results showed that voluntary running delayed the death of retinal ganglion cells vulnerable to primary degeneration but not those to secondary degeneration. In addition, voluntary running decreased the expression of glutamine synthetase, but not the expression of p-JNKs and MnSOD in the superior retina after partial optic nerve transection. These results illustrated that primary degeneration of retinal ganglion cells might be mainly related with excitotoxicity rather than oxidative stress; and the voluntary running could down-regulate excitotoxicity to delay the primary degeneration of retinal ganglion cells after partial optic nerve transection.
跑步被认为对人类健康有益。许多研究聚焦于自愿跑步对动物模型的神经保护作用。神经退行性疾病（包括青光眼）存在原发性和继发性变性。然而，跑步是否能延缓原发性或继发性变性，或者两者都能延缓，尚不清楚。部分视神经横断模型是研究原发性和继发性变性的一种有价值的青光眼模型，因为它可以将原发性变性（主要在上视网膜）与继发性变性（主要在下视网膜）区分开来。因此，我们比较了斯普拉格 - 道利大鼠跑步组和非跑步组上、下视网膜中视网膜神经节细胞的存活情况。兴奋性毒性、氧化应激和细胞凋亡参与了青光眼视网膜神经节细胞的变性过程。所以我们还采用蛋白质免疫印迹法比较了部分视神经横断后跑步组和非跑步组中一些与细胞凋亡（磷酸化 c - 原癌基因蛋白激酶，p - JNKs）、氧化应激（锰超氧化物歧化酶，MnSOD）和兴奋性毒性（谷氨酰胺合成酶）相关的蛋白质表达。结果显示，自愿跑步延缓了易发生原发性变性的视网膜神经节细胞的死亡，但对易发生继发性变性的细胞无效。此外，自愿跑步降低了部分视神经横断后上视网膜中谷氨酰胺合成酶的表达，但未降低 p - JNKs 和 MnSOD 的表达。这些结果表明，视网膜神经节细胞的原发性变性可能主要与兴奋性毒性而非氧化应激有关；自愿跑步可下调兴奋性毒性，从而延缓部分视神经横断后视网膜神经节细胞的原发性变性。
