Lira-Diaz Eduardo, Monroy-Rodriguez Jesus, Gonzalez-Pedroza Maria G, Morales-Luckie Raul A, Castro-Sánchez Luis, Gonzalez-Perez Oscar
Laboratory of Neuroscience, School of Psychology, University of Colima, Colima 28040, Mexico.
Physiological Science PhD Program, School of Medicine, University of Colima, Colima 28040, Mexico.
Life (Basel). 2022 Feb 23;12(3):333. doi: 10.3390/life12030333.
Current pharmacological therapies against demyelinating diseases are not quite satisfactory to promote remyelination. Epidermal growth factor (EGF) can expand the population of oligodendrocyte precursor cells (OPCs) that may help with the remyelination process, but its delivery into the injured tissue is still a biomedical challenge. Gold nanoparticles (GNPs) may be a useful tool for drug delivery into the brain. To evaluate remyelination in the septal nucleus, we administered intracerebral GNPs coupled with EGF (EGF-GNPs). C57BL6/J mice were demyelinated with 0.4% cuprizone (CPZ) and divided into several groups: Sham, Ctrl, GNPs, EGF, and EGF-GNPs. We evaluated the remyelination process at two time-points: 2 weeks and 3 weeks post-injection (WPI) of each treatment. We used the rotarod for evaluating motor coordination. Then, we did a Western blot analysis myelin-associated proteins: CNPase, MAG, MOG, and MBP. EGF-GNPs increase the expression of CNPase, MAG, and MOG at 2 WPI. At 3 WPI, we found that the EGF-GNPs treatment improves motor coordination and increases MAG, MOG, and MBP. EGF-GNPs enhance the expression of myelin-associated proteins and improve the motor coordination in mice. Thus, EGF-associated GNPs may be a promising pharmacological vehicle for delivering long-lasting drugs into the brain.
目前针对脱髓鞘疾病的药物治疗在促进髓鞘再生方面并不十分令人满意。表皮生长因子（EGF）可以扩大少突胶质前体细胞（OPC）的数量，这可能有助于髓鞘再生过程，但其向损伤组织的递送仍然是一个生物医学挑战。金纳米颗粒（GNP）可能是一种将药物递送至大脑的有用工具。为了评估隔核中的髓鞘再生情况，我们给予了与EGF偶联的脑内GNP（EGF-GNP）。将C57BL6/J小鼠用0.4%的铜螯合剂（CPZ）诱导脱髓鞘，并分为几组：假手术组、对照组、GNP组、EGF组和EGF-GNP组。我们在每次治疗注射后2周和3周这两个时间点评估髓鞘再生过程。我们使用转棒试验评估运动协调性。然后，我们对髓鞘相关蛋白进行了蛋白质印迹分析：2',3'-环核苷酸3'-磷酸二酯酶（CNPase）、髓鞘相关糖蛋白（MAG）、髓鞘少突胶质糖蛋白（MOG）和髓鞘碱性蛋白（MBP）。在注射后2周，EGF-GNP增加了CNPase、MAG和MOG的表达。在注射后3周，我们发现EGF-GNP治疗改善了运动协调性，并增加了MAG、MOG和MBP。EGF-GNP增强了髓鞘相关蛋白的表达并改善了小鼠的运动协调性。因此，与EGF相关的GNP可能是一种将长效药物递送至大脑的有前景的药物载体。
