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氯马斯汀对老化小鼠视神经髓鞘再生和视功能的改善作用
Clemastine improves optic nerve myelin sheath regeneration and visual function in aged mice
- 陆军军医大学学报 2022年44卷第23期 页码：2377-2383
- 作者机构：
1.400042 重庆，陆军特色医学中心眼科
2.400038 重庆，陆军军医大学(第三军医大学)基础医学院组织胚胎学教研室
- 作者简介：
[叶剑，E-mail：yejian1979@163.comYE Jian, E-mail: yejian1979@163.com
- 基金信息：
DOI：10.16016/j.2097-0927.202209207
中图分类号： R339.34;R774.6;R976收稿：2022-09-23，
修回：2022-11-18，
纸质出版：2022-12-15
- 稿件说明：
移动端阅览
冉旗, 陈琳, 叶剑. 氯马斯汀对老化小鼠视神经髓鞘再生和视功能的改善作用[J]. 陆军军医大学学报, 2022,44(23):2377-2383.
Qi RAN, Lin CHEN, Jian YE. Clemastine improves optic nerve myelin sheath regeneration and visual function in aged mice[J]. Journal of Army Medical University, 2022, 44(23): 2377-2383.
冉旗, 陈琳, 叶剑. 氯马斯汀对老化小鼠视神经髓鞘再生和视功能的改善作用[J]. 陆军军医大学学报, 2022,44(23):2377-2383. DOI： 10.16016/j.2097-0927.202209207.
Qi RAN, Lin CHEN, Jian YE. Clemastine improves optic nerve myelin sheath regeneration and visual function in aged mice[J]. Journal of Army Medical University, 2022, 44(23): 2377-2383. DOI： 10.16016/j.2097-0927.202209207.
摘要
目的
2
探究小鼠老化过程中视神经新生髓鞘的改变，及促髓鞘形成药物氯马斯汀对小鼠老化过程中视觉传导功能的影响。
方法
2
利用Cspg4-CreERt; mT/mG报告基因小鼠标记新生髓鞘，将报告基因和野生型小鼠分别分为4月龄和13月龄，结合免疫荧光染色和蛋白定量评估老化过程中视神经少突胶质细胞数量以及新生髓鞘变化；利用小鼠闪光视觉诱发电位实验(flash visual evoked potential，fVEP)评估老化小鼠视觉传导功能改变。利用Cspg4-CreERt; Tau-mGFP报告基因小鼠标记新生髓鞘，将13月龄Cspg4-CreERt; Tau-mGFP小鼠和野生型小鼠分别分为对照组和氯马斯汀治疗组，结合免疫荧光染色和fVEP实验，评估氯马斯汀对视神经新生髓鞘的作用以及对老化小鼠视觉传导功能的影响。
结果
2
免疫荧光染色发现，与4月龄小鼠相比，13月龄小鼠视神经少突胶质前体细胞NG2
+
区域面积无显著变化，而成熟少突胶质细胞CC1
+
细胞数量显著下降(
P
<
0.01)。蛋白定量分析显示，少突胶质前体细胞NG2蛋白表达量无明显改变。报告基因小鼠自发免疫荧光证实，13月龄小鼠视神经新生髓鞘mGFP
+
NG2
-
面积明显下降(
P
<
0.05)。小鼠fVEP实验中，13月龄小鼠P2潜伏期明显延长(
P
<
0.01)。氯马斯汀治疗组小鼠视神经新生髓鞘mGFP
+
数量明显增加(
P
<
0.05)，且P2潜伏期明显缩短(
P
<
0.01)。
结论
2
随着年龄增加，小鼠视神经新生髓鞘数量下降，视神经传导速度降低；氯马斯汀治疗后可显著改善小鼠髓鞘生成能力，进而促进视神经信号传导。
Abstract
Objective
2
To investigate the changes in myelin sheath of optic nerve in mice during the process of aging and explore the effect of clemastine
a pro-myelination drug
on visual function of aging mice.
Methods
2
The Cspg4-CreERt; mT/mG mice (4 and 13 months old) and wildtype C57/BL mice (4 and 13 months old) were employed in this study. The changes in number of oligodendrocytes (OLs) and newly-formed myelin were observed by immunofluorescence staining and quantitative immunoblotting. Their optical function was assessed with flash visual evoked potentials (fVEP). The reporter mice and wildtype mice at 13 months old were separately divided into control group and clemastine group. Immunostaining and fVEP test were used to observe the effects of clemastine on the newly-formed myelin and optical function.
Results
2
There was no significant difference in the density of NG2
+
cells (oligodendrocyte precursor cells
OPCs) in the 13-month-old group in comparison with the 4-month-old group
but the count of CC1
+
cells (mature OLs) was obviously decreased in the 13-month-old group (
P
<
0.01)
and immunoblotting test also showed NG2
+
protein level had no change between the groups. Immunofluorescence staining indicated that the area of mGFP
+
NG2
-
(new myelin sheath) was declined greatly in the 13-month-old reporter mice (
P
<
0.05). fVEP test suggested that the latency of P2 wave was significantly prolonged in the 13-month-old group as compared with the 4-month-old group (
P
<
0.01). Clemastine treatment resulted in notably increased mGFP
+
area (new myelin sheath) in the reporter mice (
P
<
0.05)
and remarkably shorten the latency of P2 wave in 13-month-old mice (
P
<
0.01).
Conclusion
2
Inhibited myelinogenesis and decreased nerve conduction velocity in optic nerve are observed in aging mice. Clemastine treatment can greatly improve myelinogenesis and promote conduction velocity in optic nerve.
关键词
Keywords
references
LU Y C, BROMMER B, TIAN X, et al . Reprogramming to recover youthful epigenetic information and restore vision[J ] . Nature, 2020, 588(7836): 124-129. DOI:10.1038/s41586-020-2975-4.
BLAZSÓ G, GÁBOR M. Evaluation of the anti-oedematous effects of some H1-receptor antagonists and methysergide in rats[J]. Pharmacol Res, 1997, 35(1): 65-71. DOI:10.1006/phrs.1996.0104.
GREEN A J, GELFAND J M, CREE B A, et al . Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial[J ] . Lancet, 2017, 390(10111): 2481-2489. DOI:10.1016/S0140-6736(17)32346-2.
WANG F, YANG Y J, YANG N, et al . Enhancing oligodendrocyte myelination rescues synaptic loss and improves functional recovery after chronic hypoxia[J ] . Neuron, 2018, 99(4): 689-701. e5. DOI:10.1016/j.neuron.2018.07.017.
MEI F, FANCY S P J, SHEN Y A, et al . Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis[J ] . Nat Med, 2014, 20(8): 954-960. DOI:10.1038/nm.3618.
WANG F, REN S Y, CHEN J F, et al . Myelin degeneration and diminished myelin renewal contribute to age-related deficits in memory[J ] . Nat Neurosci, 2020, 23(4): 481-486. DOI:10.1038/s41593-020-0588-8.
ZHANG Z, LIU W Y, HUANG Y B, et al . NLRP3 deficiency attenuat es secondary degeneration of visual cortical neurons following optic nerve injury[J ] . Neurosci Bull, 2020, 36(3): 277-288. DOI:10.1007/s12264-019-00445-x.
STADELMANN C, TIMMLER S, BARRANTES-FREER A, et al . Myelin in the central nervous system: structure, function, and pathology[J ] . Physiol Rev, 2019, 99(3): 1381-1431. DOI:10.1152/physrev.00031.2018.
BEHRANGI N, LORENZ P, KIPP M. Oligodendrocyte lineage marker expression in eGFP-GFAP transgenic mice[J]. J Mol Neurosci, 2021, 71(11): 2237-2248. DOI:10.1007/s12031-020-01771-w.
TRIPATHI R B, JACKIEWICZ M, MCKENZIE I A, et al . Remarkable stability of myelinating oligodendrocytes in mice[J ] . Cell Rep, 2017, 21(2): 316-323. DOI:10.1016/j.celrep.2017.09.050.
BAO C C, HE C Q, SHU B, et al . Aerobic exercise training decreases cognitive impairment caused by demyelination by regulating ROCK signaling pathway in aging mice[J ] . Brain Res Bull, 2021, 168: 52-62. DOI:10.1016/j.brainresbull.2020.12.010.
LUBLIN F D, HÄRING D A, GANJGAHI H, et al . How patients with multiple sclerosis acquire disability[J ] . Brain, 2022, 1 45(9): 3147-3161. DOI:10.1093/brain/awac016.
MCKENZIE I A, OHAYON D, LI H L, et al . Motor skill learning requires active central myelination[J ] . Science, 2014, 346(6207): 318-322. DOI:10.1126/science.1254960.
XIAO L, OHAYON D, MCKENZIE I A, et al . Rapid production of new oligodendrocytes is required in the earliest stages of motor-skill learning[J ] . Nat Neurosci, 2016, 19(9): 1210-1217. DOI:10.1038/nn.4351.
MONIE M. Myelin Plasticity and Nervous System Function[J]. Annu Rev Neurosci, 2018, 41: 61-76. DOI: 10.1146/annurev-neuro-080317-061853
ARRUDA J E, MCINNIS M C, STEELE J. The flash visual evoked potential-P2 and the detection of amnestic mild cognitive impairment: a review of empirical literature[J]. Int J Psychophysiol, 2020, 155: 162-167. DOI:10.1016/j.ijpsycho.2020.05.012.
MARENNA S, CASTOLDI V, D'ISA R, et al . Semi-invasive and non-invasive recording of visual evoked potentials in mice[J ] . Doc Ophthalmol, 2019, 138(3): 169-179. DOI:10.1007/s10633-019-09680-z.
NAJM F J, MADHAVAN M, ZAREMBA A, et al . Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo [J ] . Nature, 2015, 522(7555): 216-220. DOI:10.1038/nature14335..
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