Effects of Transplanted Umbilical Cord Blood Mononuclear Cells Overexpressing GDNF on Spatial Memory and Hippocampal Synaptic Proteins in a Mouse Model of Alzheimer's Disease
| Autor: | Albert A. Rizvanov, M. Kaligin, Ilnur I. Salafutdinov, A. V. Leushina, Yana O. Mukhamedshina, Andrey L. Zefirov, Marat A. Mukhamedyarov, Ekaterina E. Garanina, Helton José Reis, Elena Petukhova, András Palotás |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Synaptogenesis Synaptophysin Mice Transgenic Hippocampal formation Neuroprotection Hippocampus 03 medical and health sciences Mice 0302 clinical medicine Neurotrophic factors Alzheimer Disease Pregnancy medicine Glial cell line-derived neurotrophic factor Animals Humans Glial Cell Line-Derived Neurotrophic Factor Spatial Memory biology General Neuroscience Neurodegeneration General Medicine medicine.disease Transplantation Psychiatry and Mental health Clinical Psychology Disease Models Animal 030104 developmental biology HEK293 Cells nervous system biology.protein Cancer research Female Cord Blood Stem Cell Transplantation Geriatrics and Gerontology Disks Large Homolog 4 Protein 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's disease : JAD. 69(2) |
| ISSN: | 1875-8908 |
| Popis: | Background/objective Alzheimer's disease (AD) is a progressive incurable neurodegenerative disorder. Glial cell line-derived neurotrophic factor (GDNF) is a prominent regulator of brain tissue and has an impressive potential for use in AD therapy. While its metabolism is still not fully understood, delivering neuropeptides such as GDNF via umbilical cord blood mononuclear cells (UCBMCs) to the sites of neurodegeneration is a promising approach in the development of innovative therapeutic avenues. Methods UCBMCs were transduced with adenoviral vectors expressing GDNF and injected into AD transgenic mice. Various parameters including homing and survival of transplanted cells, expression of GDNF and synaptic proteins, as well as spatial memory were evaluated. Results UCBMCs were observed in the hippocampus and cortex several weeks after transplantation, and their long-term presence was associated with improved spatial memory. Post-synaptic density protein 95 (PSD-95) and synaptophysin levels in the hippocampus were also effectively restored following the procedure in AD mice. Conclusions Our data indicate that gene-cell therapy with GDNF-overexpressing UCBMCs may produce long-lasting neuroprotection and stimulation of synaptogenesis. Such adenoviral constructs could potentially possess a high therapeutic potential for the treatment of AD. |
| Databáze: | OpenAIRE |
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