Dahmardeh Narjes, Shabani Mohammad, Basiri Mohsen, Kalantaripour Taj Pari, Asadi-Shekaari Majid
Department of Anatomical Sciences, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran.
Department of Anatomical Sciences, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran.
Malays J Med Sci. 2019 Jul;26(4):28-38. doi: 10.21315/mjms2019.26.4.4. Epub 2019 Aug 29.
There is a meaningful necessity for a targeted therapy of essential tremor (ET), as medications have not been developed specifically for ET. For nearly a century, many drugs have been applied in the treatment of tremor but the drug treatment of ET remains still unknown. Some potential therapeutic factors such fingolimod (FTY720) can be effectively used to treat ET in animals. In the present research, the effect of FTY720, the immunomodulatory sphingosine 1-phosphate (S1P) analog, on degeneration of cerebellar and olivary neurons induced by harmaline in male rats was investigated.
The animals were allotted into control dimethyl sulfoxide (DMSO), saline + harmaline [30 mg/kg, intraperitoneally, (i.p.)], harmaline + FTY720 (1 mg/kg, i.p, 1 h and 24 h before harmaline injection) groups ( = 10). The cerebellum and inferior olive nucleus (ION) were studied for neuronal degeneration using immunohistochemistry (IHC) and ultrastructural study by transmission electron microscopy (TEM) techniques.
Harmaline caused neuronal cell loss, caspase-3 mediated apoptosis, astrocytosis and ultrastructural changes in cerebellar Purkinje cells and inferior olive neurons. FTY720 exhibited neuroprotective effects on cerebellar Purkinje cells and inferior olivary neurons.
These results suggest that FTY720 has potential efficacy for prevention of ET neurodegeneration and astrocytosis induced by harmaline in male rats.
由于尚未开发出专门用于治疗特发性震颤（ET）的药物，因此对ET进行靶向治疗具有重要意义。近一个世纪以来，许多药物已被应用于震颤治疗，但ET的药物治疗仍然未知。一些潜在的治疗因素，如芬戈莫德（FTY720），可有效用于治疗动物的ET。在本研究中，研究了免疫调节性鞘氨醇-1-磷酸（S1P）类似物FTY720对雄性大鼠中由harmaline诱导的小脑和橄榄神经元变性的影响。
将动物分为对照二甲亚砜（DMSO）组、生理盐水+harmaline[30mg/kg，腹腔注射，（i.p.）]组、harmaline+FTY720（1mg/kg，i.p，在harmaline注射前1小时和24小时）组（每组n = ）。使用免疫组织化学（IHC）和透射电子显微镜（TEM）技术进行超微结构研究，以研究小脑和下橄榄核（ION）中的神经元变性。
Harmaline导致小脑浦肯野细胞和下橄榄神经元的神经元细胞丢失、caspase-3介导的细胞凋亡、星形细胞增多和超微结构变化。FTY720对小脑浦肯野细胞和下橄榄神经元具有神经保护作用。
这些结果表明，FTY720在预防雄性大鼠中由harmaline诱导的ET神经变性和星形细胞增多方面具有潜在疗效。
