Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
J Chem Neuroanat. 2020 Dec;110:101865. doi: 10.1016/j.jchemneu.2020.101865. Epub 2020 Sep 28.
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.
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 × 10 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.
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).
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.
实验研究表明，干细胞移植是治疗帕金森病（PD）的一种方法。在本研究中，我们观察了人脐带来源的间充质干细胞（hWJ-MSCs）单独应用和与 l-多巴联合应用对 PD 大鼠模型记忆障碍的修复作用。
将 50 只成年雄性 Wistar 大鼠随机分为五组：1）假手术组，2）PD 组，3）PD+C 组，4）PD+C+D 组和 5）PD+D 组。PD 模型通过向内侧前脑束（MFB）注射 6-羟多巴胺（16 μg/2 μl）诱导，并在诱导后 14 天通过注射阿朴吗啡诱导出现对侧旋转来确认。大鼠在 PD 诱导后第 14 天和第 28 天接受两次 hWJ-MSCs（1×10 个细胞，静脉注射）治疗。治疗后的 PD 大鼠单独或联合应用 l-多巴和卡比多巴（10/30 mg/kg，腹腔注射）。四个月后，评估记忆、海马长时程增强（hLTP）、组织学变化以及纹状体中脑源性神经营养因子（BDNF）和神经生长因子（NGF）的水平。
PD 导致颗粒层细胞丢失和细胞核染色变深，纹状体中 BDNF 和 NGF 水平显著降低（P<0.001）。这些病理改变与记忆和 hLTP 缺陷相关（分别为 P<0.001）。单独应用 hWJ-MSCs（P<0.05 和 P<0.001）以及联合应用 l-多巴（P<0.001）治疗 PD 大鼠可显著恢复两种神经营养因子的水平，随后改善认知和 hLTP（P<0.001）。
本研究结果表明，单独或联合应用 l-多巴慢性治疗 PD 大鼠可通过重建多巴胺能神经元和提高 BDNF 和 NGF 因子来恢复记忆和 hLTP。
