Tahmasebi Fatemeh, Asl Elmira Roshani, Faghihi Faezeh, Bolandi Nadia, Barati Shirin
Department of Anatomy, Saveh University of Medical Sciences, Saveh, Iran.
Department of Biochemistry, Saveh University of Medical Sciences, Saveh, Iran.
Cell Mol Neurobiol. 2025 May 2;45(1):40. doi: 10.1007/s10571-025-01558-w.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Stem cells as a source of neurotrophic factors and ellagic acid (EA) as an antioxidant reduce the progression of neurodegenerative diseases. In this study, we evaluated the effect of olfactory ecto-mesenchymal stem cell (EMSC) supernatant and EA on A1 astrocytes, M1 microglia, and demyelination in cuprizone model. To induce the chronic demyelination model, mice received a diet containing 0.2% cuprizone/kg of food for 12 weeks. EMSC supernatant was injected into the lateral ventricle of mice. EA was administered intraperitoneally daily at a dose of 80 mg/kg body weight for two weeks. Two weeks after injection, immunohistochemistry was performed to detect the presence of astrocytes (GFAP), microglia/macrophages (Iba-1), and oligodendrocytes (Olig2). The level of gene expression of EMSC (TGF-β and BDNF), astrocytes (C3 and GBP2) and microglia (iNOS, TNF-α and IL-6) was evaluated by qRT-PCR method. The results showed that injection of EMSC and EA increased the expression of TGF-β and BDNF genes as trophic factors. LFB images showed that supernatant and EA significantly improved remyelination, which was accompanied by an increase in oligodendrocyte population. The astrocyte population increased in the cuprizone group, while it decreased after supernatant and EA administration. The supernatant and EA decreased microglia after cuprizone induction. The qRT-PCR showed neurotoxic genes of A1 and M1 decreased after supernatant and EA administration. Here, we demonstrate that EMSC supernatant and EA could improve demyelination in neurodegenerative diseases such as MS by reducing microgliosis and astrocytosis in addition to increasing myelination.
多发性硬化症（MS）是一种中枢神经系统的炎症性脱髓鞘疾病。干细胞作为神经营养因子的来源，而鞣花酸（EA）作为一种抗氧化剂，可减少神经退行性疾病的进展。在本研究中，我们评估了嗅球外间充质干细胞（EMSC）上清液和EA对铜螯合剂模型中A1星形胶质细胞、M1小胶质细胞和脱髓鞘的影响。为诱导慢性脱髓鞘模型，给小鼠喂食含0.2%铜螯合剂/千克食物的饲料，持续12周。将EMSC上清液注入小鼠侧脑室。EA以80毫克/千克体重的剂量每日腹腔注射，持续两周。注射两周后，进行免疫组织化学检测星形胶质细胞（GFAP）、小胶质细胞/巨噬细胞（Iba-1）和少突胶质细胞（Olig2）的存在情况。通过qRT-PCR方法评估EMSC（TGF-β和BDNF）、星形胶质细胞（C3和GBP2）和小胶质细胞（iNOS、TNF-α和IL-6）的基因表达水平。结果表明，注射EMSC和EA可增加作为营养因子的TGF-β和BDNF基因的表达。LFB图像显示，上清液和EA显著改善了髓鞘再生，同时少突胶质细胞数量增加。铜螯合剂组星形胶质细胞数量增加，而上清液和EA给药后数量减少。铜螯合剂诱导后，上清液和EA减少了小胶质细胞数量。qRT-PCR显示，上清液和EA给药后，A1和M1的神经毒性基因减少。在此，我们证明，EMSC上清液和EA除了增加髓鞘形成外，还可通过减少小胶质细胞增生和星形胶质细胞增生来改善MS等神经退行性疾病中的脱髓鞘。
