Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Department of Traditional Medicine, Chang Gung University, Guishan, Taoyuan 333, Taiwan.
Int J Mol Sci. 2021 Jun 23;22(13):6718. doi: 10.3390/ijms22136718.
With the improvement of the survival rate of acute lymphoblastic leukemia (ALL) in children, some children ALL survivors reveal inferior intellectual and cognition outcome. Methotrexate (MTX), while serving as an essential component in ALL treatment, has been reported to be related to various neurologic sequelae. Using combined intrathecal (IT) and intraperitoneal (IP) MTX model, we had demonstrated impaired spatial memory function in developing rats, which can be rescued by melatonin treatment. To elucidate the impact of MTX treatment on the epigenetic modifications of the myelination process, we examined the change of neurotrophin and myelination-related transcriptomes in the present study and found combined IT and IP MTX treatment resulted in altered epigenetic modification on the myelination process, mainly in the hippocampus. Further, melatonin can restore the MTX effect through alterations of the epigenetic pathways.
随着儿童急性淋巴细胞白血病（ALL）存活率的提高，一些儿童 ALL 幸存者的智力和认知结果较差。甲氨蝶呤（MTX）作为 ALL 治疗的重要组成部分，据报道与各种神经后遗症有关。使用鞘内（IT）和腹腔内（IP）MTX 联合模型，我们已经证明在发育中的大鼠中存在空间记忆功能受损，而褪黑素治疗可以挽救这种功能受损。为了阐明 MTX 治疗对髓鞘形成过程中表观遗传修饰的影响，我们在本研究中检查了神经营养因子和髓鞘形成相关转录组的变化，发现联合 IT 和 IP MTX 治疗导致髓鞘形成过程中的表观遗传修饰改变，主要在海马体中。此外，褪黑素可以通过改变表观遗传途径来恢复 MTX 的作用。
