Effectiveness of Insulin-Induced umbilical cord stem cells on Seladin-1/APP/GFAP expression in rat hippocampal CA1/CA3 regions following chronic hypoxia

IF 2.2 4区 生物学 Q3 CELL BIOLOGY
Gholamreza Hassanzadeh, Soheil Ashouri, Reza Kargar, Atefeh Shamosi, Simin Mahakizadeh
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引用次数: 0

Abstract

Dementia, a syndrome characterized by cognitive impairment, significantly impacts the global elderly population. Given their paracrine properties, mesenchymal stem cells (MSCs) represent a promising avenue for developing novel treatments for neurodegenerative disorders. Chronic hypoxia models Alzheimer’s disease-like pathology by triggering neuroinflammation and altering key biomarkers. This study evaluated the therapeutic potential of MSCs, insulin-induced MSCs, and insulin in a rat model of Alzheimer’s disease (AD). Forty-eight rats were allocated into eight experimental groups: normoxic control, sham-surgery control, and six hypoxic intervention groups (exposed to 8% O₂). Intraventricular administration of MSCs or insulin-induced MSCs, intranasal administration of insulin, or both insulin and MSCs were used in the intervention groups. Hypoxic exposure significantly elevated pro-inflammatory cytokines (IL-1β, TNF-α) and increased expression of glial fibrillary acidic protein (GFAP) and amyloid precursor protein (APP), while decreasing levels of the neuroprotective factor Seladin-1. Administration of MSCs or Ins-MSCs effectively mitigated these hypoxia-induced alterations. Specifically, treatment with MSCs or Insulin induced-MSCs restored Seladin-1, GFAP, and APP expression levels to those observed in normoxic controls. Furthermore, these treatments attenuated the hypoxia-associated increase in Nissl body pathology within the hippocampal pyramidal cell layer. The most pronounced therapeutic benefits were observed following combined intranasal insulin and intraventricular MSC administration. Consequently, the combinatorial approach of MSCs and insulin warrants further investigation as a potential therapeutic strategy for Alzheimer’s disease. Combining intranasal insulin with insulin-induced MSCs may offer a strategy to target multiple AD pathology pathways.

Abstract Image

Abstract Image

胰岛素诱导脐带干细胞对慢性缺氧大鼠海马CA1/CA3区Seladin-1/APP/GFAP表达的影响
痴呆症是一种以认知障碍为特征的综合征,严重影响着全球老年人口。鉴于其旁分泌特性,间充质干细胞(MSCs)代表了开发神经退行性疾病新疗法的有希望的途径。慢性缺氧通过触发神经炎症和改变关键生物标志物来模拟阿尔茨海默病样病理。本研究评估了间充质干细胞、胰岛素诱导间充质干细胞和胰岛素在阿尔茨海默病(AD)大鼠模型中的治疗潜力。48只大鼠被分为8个实验组:常氧对照组、假手术对照组和6个低氧干预组(暴露于8% O₂)。干预组采用脑室内给药MSCs或胰岛素诱导的MSCs,鼻内给药胰岛素,或胰岛素和MSCs同时给药。低氧暴露显著升高促炎因子(IL-1β、TNF-α),增加胶质纤维酸性蛋白(GFAP)和淀粉样蛋白前体蛋白(APP)的表达,同时降低神经保护因子Seladin-1的水平。给药MSCs或Ins-MSCs有效地减轻了这些缺氧引起的改变。具体来说,用MSCs或胰岛素诱导的MSCs治疗可使Seladin-1、GFAP和APP的表达水平恢复到正常对照组的水平。此外,这些治疗减轻了缺氧相关的海马锥体细胞层内尼氏体病理的增加。鼻内胰岛素和脑室间充质干细胞联合给药后观察到最明显的治疗效果。因此,MSCs和胰岛素的组合方法值得进一步研究,作为阿尔茨海默病的潜在治疗策略。将鼻内胰岛素与胰岛素诱导的间充质干细胞联合使用可能提供针对多种阿尔茨海默病病理途径的策略。
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来源期刊
Journal of Molecular Histology
Journal of Molecular Histology 生物-细胞生物学
CiteScore
5.90
自引率
0.00%
发文量
68
审稿时长
1 months
期刊介绍: The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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