EFFECT OF TRANSPLANTATION OF HUMAN UMBILICAL CORD BLOOD MONONUCLEAR CELLS OVEREXPRESSING GLIAL NEUROTROPHIC FACTOR ON THE STATE OF MICROGLIA AND ASTROCYTES IN TRANSGENIC MICE WITH ALZHEIMER'S DISEASE MODEL

E. Petukhova, Y. Mukhamedshina, A. Timofeeva, A. Rizvanov, M. Mukhamedyarov
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Abstract

Introduction. Alzheimer's disease is a neurodegenerative disease characterized by a progressive decline in cognitive functions. Alzheimer’s disease is the most common form of dementia and one of the main causes of disability in older people. Neuroinflammation is an important factor in the pathogenesis of Alzheimer's disease. The neuroinflammatory reaction observed in Alzheimer's disease is primarily caused by resident immune cells of the central nervous system, including microglia and astrocytes. Aim. The aim of this work was to study the effect of transplantation of human umbilical cord blood mononuclear cells (UCBMC) overexpressing glial neurotrophic factor (GDNF) on the state of microglia and astrocytes in APP/PS1 transgenic mice with Alzheimer's disease model. Material and methods. Xenotransplantation of gene-cell structures to experimental animals was carried out retroorbitally, once in the amount of 2 million cells. Immunofluorescence examination of cryostatic sections of the brain was carried out by applying antibodies to ionized calcium-binding adaptive molecule 1 (Iba1, marker of microglia and macrophages) and antibodies to glial fibrillar acid protein (GFAP, marker of astrocytes) and subsequent imaging on a confocal scanning microscope LSM 510-Meta (Carl Zeiss). Results and discussion. It was found that transplantation of UCBMC overexpressing GDNF reduced the severity of microgliosis in the parietal cortex and dentate gyrus of the hippocampus, and also reduced the severity of astrogliosis in the CA3 zone of the hippocampus of the brain of APP/PS1 mice. Transplantation of UCBMC overexpressing enhanced green fluorescent protein (EGFP) only reduced the severity of microgliosis in the parietal cortex of APP/PS1 mice. Conclusion. The data obtained indicate a high therapeutic potential of transplantation of UCBMC overexpressing GDNF in Alzheimer's neuropathology.
人脐带血过表达胶质神经营养因子的单核细胞移植对阿尔茨海默病转基因小鼠小胶质细胞和星形胶质细胞状态的影响
介绍。阿尔茨海默病是一种神经退行性疾病,其特征是认知功能的进行性下降。阿尔茨海默病是最常见的痴呆症,也是老年人残疾的主要原因之一。神经炎症是阿尔茨海默病发病的重要因素。在阿尔茨海默病中观察到的神经炎症反应主要是由中枢神经系统的常驻免疫细胞引起的,包括小胶质细胞和星形胶质细胞。的目标。本研究旨在研究过表达胶质神经营养因子(GDNF)的人脐带血单个核细胞(UCBMC)移植对APP/PS1转基因阿尔茨海默病模型小鼠小胶质细胞和星形胶质细胞状态的影响。材料和方法。对实验动物进行基因细胞结构的眶后异种移植,每次移植200万个细胞。应用离子钙结合适应性分子1 (Iba1,小胶质细胞和巨噬细胞的标记物)抗体和胶质纤维酸蛋白(GFAP,星形胶质细胞的标记物)抗体,在共聚焦扫描显微镜LSM 510-Meta(卡尔蔡司)上成像,对大脑冷冻切片进行免疫荧光检查。结果和讨论。结果发现,移植过表达GDNF的UCBMC可降低APP/PS1小鼠海马顶叶皮层和齿状回小胶质瘤的严重程度,也可降低APP/PS1小鼠大脑海马CA3区星形胶质瘤的严重程度。过表达增强型绿色荧光蛋白(EGFP)的UCBMC移植仅能降低APP/PS1小鼠顶叶皮层小胶质瘤的严重程度。结论。所获得的数据表明,移植过表达GDNF的UCBMC在阿尔茨海默病神经病理学中具有很高的治疗潜力。
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