Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
J Chem Neuroanat. 2021 Apr;113:101921. doi: 10.1016/j.jchemneu.2021.101921. Epub 2021 Feb 15.
Human Wharton's jelly-derived Mesenchymal Stromal Cells (hWJ-MSCs) have shown beneficial effects in improving the dopaminergic cells in the Parkinson's disease (PD). In the present study, the effects of hWJ-MSCs on hyperalgesia, anxiety deficiency and Pallidal local electroencephalogram (EEG) impairment, alone and combined with L-dopa, were examined in a rat model of PD. Adult male Wistar rats were divided into five groups: 1) sham, 2) PD, 3) PD + C (Cell therapy), 4) PD + C+D (Drug), and 5) PD + D. PD was induced by injection of 6-OHDA (16 μg/2 μl into medial forebrain bundle (MFB)). PD + C group received hWJ-MSCs (1 × 10 cells, intravenous (i.v.)) twice post PD induction. PD + C+D groups received hWJ-MSCs combined with L-Dopa/Carbidopa, (10/30 mg/kg, intraperitoneally (i.p.)). PD + D group received L-Dopa/Carbidopa alone. Four months later, analgesia, anxiety-like behaviors, were evaluated and Pallidal local EEG was recorded. Level of insulin-like growth factor 1 (IGF-1) was measured in the striatum and dopaminergic neurons were counted in substantia nigra (SNc). According to data, MFB-lesioned rats showed hyperalgesia in tail flick, anxiety-like symptoms in cognitive tests, impairment of electrical power of pallidal local EEG as field potential, count of dopaminergic neurons in SNc and level of IGF-1 in striatum. These complications restored significantly by MSCs treatment (p < 0.001). Our findings confirm that chronic treatment with hWJ-MSC, alone and in combination with L-Dopa, improved nociception and cognitive deficit in PD rats which may be the result of increasing IGF-1 and protect the viability of dopaminergic neurons.
人牙髓间充质基质细胞（hWJ-MSCs）已显示出在改善帕金森病（PD）中的多巴胺能细胞方面的有益作用。在本研究中，我们在 PD 大鼠模型中检查了 hWJ-MSCs 对痛觉过敏、焦虑缺乏和苍白球局部脑电图（EEG）损伤的单独作用以及与 L-多巴联合作用。成年雄性 Wistar 大鼠分为五组：1）假手术组，2）PD 组，3）PD+C（细胞治疗组），4）PD+C+D（药物组）和 5）PD+D 组。PD 通过向中脑边缘束（MFB）内注射 6-OHDA（16μg/2μl）诱导。PD+C 组在 PD 诱导后两次接受 hWJ-MSCs（1×10 个细胞，静脉内（i.v.））。PD+C+D 组接受 hWJ-MSCs 联合 L-多巴/卡比多巴（10/30mg/kg，腹腔内（i.p.））。PD+D 组单独接受 L-多巴/卡比多巴。四个月后，评估镇痛、焦虑样行为，并记录苍白球局部 EEG。纹状体中胰岛素样生长因子 1（IGF-1）的水平，以及黑质（SNc）中的多巴胺能神经元的计数。根据数据，MFB 损伤大鼠在尾巴摆动时出现痛觉过敏，在认知测试中出现焦虑样症状，苍白球局部 EEG 的电功率作为场电位受损，SNc 中的多巴胺能神经元计数和纹状体中的 IGF-1 水平降低。这些并发症通过 MSC 治疗显著恢复（p<0.001）。我们的发现证实，慢性给予 hWJ-MSC，单独给予或与 L-多巴联合给予，可改善 PD 大鼠的痛觉和认知缺陷，这可能是 IGF-1 增加和保护多巴胺能神经元活力的结果。
