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Transplanted Wharton`s jelly mesenchymal stem cells improve memory and brain hippocampal electrophysiology in rat model of Parkinson’s disease
Journal of Chemical Neuroanatomy ( IF 2.8 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.jchemneu.2020.101865
Maryam Sadat Jalali , Alireza Sarkaki , Yaghoub Farbood , Seyed saeed Azandeh , Esrafil Mansouri , Mohammad Ghasemi dehcheshmeh , Ghasem Saki

BACKGROUND Experimental findings have shown that stem cell transplantation is a therapeutic procedure for Parkinson's disease (PD). In this study, effects of human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs), alone and combined with L-dopa, were examined for repairing memory impairment in a rat model of PD. METHODS Fifty adult male Wistar rats were randomly divided into five groups: 1) sham, 2) PD, 3) PD + C, 4) PD + C+D, and 5) PD + D. PD was induced by 6-OHDA injection (16 μg/2 μl) into medial forebrain bundle (MFB) and was confirmed 14 days later by contralateral rotation using apomorphine injection. The rats received hWJ-MSCs (1 × 106 cells, i.v.) twice on the 14th and 28th days post PD induction. Treated PD rats received hWJ-MSCs alone or combined with L-Dopa and Carbidopa (10/30 mg/kg, i.p.). Four months later, memory, hippocampal long-term potentiation (hLTP), histological changes, and the levels of BDNF and NGF in striatum were evaluated. RESULTS PD caused both cell loss with small dark stained nuclei in granular zone as well as significant decrement of BDNF and NGF (P < 0.001) in striatum. These pathological alterations were associated with memory and hLTP deficits (P < 0.001 respectively). Treating PD rats with hWJ-MSCs, alone (P < 0.05 and P < 0.001) and combined with L-Dopa (P < 0.001), significantly restored the levels of both of the neurotrophins followed by improving cognition and hLTP (P < 0.001). CONCLUSION Current findings showed that chronic treatment of PD rats with hWJ-MSCs, alone and in combination with L-Dopa, could restore memory and hLTP by reconstructing dopaminergic neurons and elevating the BDNF and NGF factors.

中文翻译:

移植沃顿果冻间充质干细胞改善帕金森病大鼠模型的记忆力和脑海马电生理

背景实验结果表明,干细胞移植是帕金森病(PD)的一种治疗方法。在这项研究中,研究了人类沃顿氏果冻衍生的间充质干细胞 (hWJ-MSCs) 单独和与左旋多巴联合的作用,用于修复 PD 大鼠模型中的记忆障碍。方法 50只成年雄性Wistar大鼠随机分为5组:1)sham组,2)PD组,3)PD+C组,4)PD+C+D组,5)PD+D组。6-OHDA注射诱导PD (16 μg/2 μl) 注入内侧前脑束 (MFB),并在 14 天后使用阿扑吗啡注射液通过对侧旋转进行确认。大鼠在 PD 诱导后第 14 天和第 28 天接受 hWJ-MSCs(1 × 106 个细胞,静脉注射)两次。治疗的 PD 大鼠单独接受 hWJ-MSCs 或与左旋多巴和卡比多巴 (10/30 mg/kg, ip) 组合。四个月后,记忆,评估了海马长时程增强 (hLTP)、组织学变化以及纹状体中 BDNF 和 NGF 的水平。结果 PD 导致细胞丢失,颗粒区有小的深色染色核,以及纹状体中 BDNF 和 NGF 的显着减少(P < 0.001)。这些病理改变与记忆和 hLTP 缺陷有关(分别为 P < 0.001)。用 hWJ-MSCs 治疗 PD 大鼠,单独(P < 0.05 和 P < 0.001)和联合左旋多巴(P < 0.001),显着恢复两种神经营养素的水平,随后改善认知和 hLTP(P < 0.001) . 结论 目前的研究结果表明,hWJ-MSCs 单独或与左旋多巴联合治疗 PD 大鼠,可以通过重建多巴胺能神经元和提升 BDNF 和 NGF 因子来恢复记忆和 hLTP。
更新日期:2020-12-01
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