ABSTRACT
<p><b>OBJECTIVE</b>To observe the migration and differentiation of the neural precursor cells (NPCs) that derived from murine embryonic stem cells (ESCs) when they were transplanted into amyloid beta (A beta)-treated rat hippocampus.</p><p><b>METHODS</b>MESPU35, a murine ESC cell line that express the enhanced green fluorescent protein (EGFP), was induced differentiation into nestin-positive NPCs by modified serum-free methods. The A beta plaques and the differentiation of the grafted cells were observed by immunofluorescent staining.</p><p><b>RESULTS</b>Comparing 16 weeks with 4 weeks post-transplantation, the migration distance increased about 5 times; the rate of migratory NPCs differentiating into glial fibrillary acidic protein (GFAP)-positive cells kept rising from (30.41+/-1.45) % to (49.25+/-1.23) %, and the rate of NPCs differentiating into neurofilament 200 (NF200) positive cells increased from (16.68+/-0.95) % to (27.94+/-1.21) %. Meanwhile, the GFAP-positive cells targeting to the ipsilateral side of A beta plaques increased from 60.2% to 81.3%, while the NF200-positive cells increased from 61.3% to 84.1%. The migration distance had significant positive linear correlations to the neuronal differentiation rate (r = 0.991) and to the astrocytic differentiation rate (r = 0.953).</p><p><b>CONCLUSION</b>Engrafted NPCs migrate targetedly to the A beta injection site and differentiate into neurons and astrocytes.</p>
Subject(s)
Animals , Male , Rats , Amyloid beta-Peptides , Metabolism , Cell Differentiation , Cell Movement , Embryonic Stem Cells , Cell Biology , Physiology , Transplantation , Fluorescent Antibody Technique , Glial Fibrillary Acidic Protein , Metabolism , Green Fluorescent Proteins , Metabolism , Hippocampus , Cell Biology , Physiology , Injections, Intraventricular , Neurons , Cell Biology , Physiology , Transplantation , Rats, Wistar , Stem Cell TransplantationABSTRACT
Objective To identify the genetype of the PS1/APP double transgenic mouse model, then to analyse the histopathological changes in the brain and compare the differences between the transgenic mice models and Abeta1-40-injected rats models of Alzheimer disease. Methods The modified congo red staining, Nissl's staining and immunohistology staimouse extensively displayed Abeta deposits, activation of astrocyte respectively. Results (1) The PS1/APP transgenic mouse extensively displayed Abeta deposits in the cortex and hippocampal structures, and GFAP positive cells were aggregated in mass and surrounded the congo red-positive plaque. (2) The Abeta1-40-intrahippocampal-injected rat model showed the Abeta plaque deposits in the dentate gyrus of the hippocampus, with the astrocyte surrounded. The neurons loss was significant in the injection point and pin hole of injection with Nissl's staining methods. GFAP-positive cells increased significantly compared with the uninjected lateral of the hippocampus. Conclusion Although Abeta1-40-injected rat models could simulate some characteristic pathological features of human Alzheimer diseases, Abeta deposits and neurons loss in partial hippocampal, it would not simulate the progressive degenenration in the brain of AD. The double transgenic PS1/APP mice could simulate the specific pathogenesis and progressive changes of AD, mainly is Abeta deposits and the spongiocyte response, while no neurons loss were observed in this model.