Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/37546 http://dx.doi.org/10.3389/fnagi.2014.00030 |
Resumo: | Alzheimer's disease (AD) is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits, such as alterations in social interactions. the major pathological features of AD are the formation of senile plaques and neurofibrillary tangles together with neuronal and vascular damage. the double transgenic mouse model of AD (2xTg-AD) with the APPswe/PS1dE9 mutations shows characteristics that are similar to those observed in AD patients, including social memory impairment, senile plaque formation and vascular deficits. Mesenchymal stem cells (MSCs), when transplanted into the brain, produce positive effects by reducing amyloid-beta (AN deposition in transgenic amyloid precursor protein (APP)/presenilins1 (PS1) mice. Vascular endothelial growth factor (VEGF), exhibits neuroprotective effects against the excitotoxicity implicated in the AD neurodegeneration. the present study investigates the effects of MSCs overexpressing VEGF in hippocampal neovascularization, cognitive dysfunction and senile plaques present in 2xTg-AD transgenic mice. MSC were transfected with vascular endothelial growth factor cloned in uP vector under control of modified CMV promoter (uP-VEGF) vector, by electroporation and expanded at the 14th passage. 2xTg-AD animals at 6, 9 and 12 months old were transplanted with MSC-VEGF or MSC. the animals were tested for behavioral tasks to access locomotion, novelty exploration, learning and memory, and their brains were analyzed by immunohistochemistry (IHC) for vascularization and A(3 plaques. MSC-VEGF treatment favored the neovascularization and diminished senile plaques in hippocampal specific layers. Consequently, the treatment was able to provide behavioral benefits and reduce cognitive deficits by recovering the innate interest to novelty and counteracting memory deficits present in these AD transgenic animals. Therefore, this study has important therapeutic implications for the vascular damage in the neurodegeneration promoted by AD. |
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Garcia, Karina de Oliveira [UNIFESP]Ornellas, Felipe Leite de Moraes [UNIFESP]Martin, Priscila Keiko Matsumoto [UNIFESP]Patti, Camilla L. [UNIFESP]Mello, Luiz Eugenio Araujo de Moraes [UNIFESP]Frussa-Filho, Roberto [UNIFESP]Han, Sang Won [UNIFESP]Longo, Beatriz Monteiro [UNIFESP]Universidade Federal de São Paulo (UNIFESP)2016-01-24T14:35:26Z2016-01-24T14:35:26Z2014-03-07Frontiers in Aging Neuroscience. Lausanne: Frontiers Research Foundation, v. 6, 15 p., 2014.1663-4365http://repositorio.unifesp.br/handle/11600/37546http://dx.doi.org/10.3389/fnagi.2014.00030WOS000332605400001.pdf10.3389/fnagi.2014.00030WOS:000332605400001Alzheimer's disease (AD) is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits, such as alterations in social interactions. the major pathological features of AD are the formation of senile plaques and neurofibrillary tangles together with neuronal and vascular damage. the double transgenic mouse model of AD (2xTg-AD) with the APPswe/PS1dE9 mutations shows characteristics that are similar to those observed in AD patients, including social memory impairment, senile plaque formation and vascular deficits. Mesenchymal stem cells (MSCs), when transplanted into the brain, produce positive effects by reducing amyloid-beta (AN deposition in transgenic amyloid precursor protein (APP)/presenilins1 (PS1) mice. Vascular endothelial growth factor (VEGF), exhibits neuroprotective effects against the excitotoxicity implicated in the AD neurodegeneration. the present study investigates the effects of MSCs overexpressing VEGF in hippocampal neovascularization, cognitive dysfunction and senile plaques present in 2xTg-AD transgenic mice. MSC were transfected with vascular endothelial growth factor cloned in uP vector under control of modified CMV promoter (uP-VEGF) vector, by electroporation and expanded at the 14th passage. 2xTg-AD animals at 6, 9 and 12 months old were transplanted with MSC-VEGF or MSC. the animals were tested for behavioral tasks to access locomotion, novelty exploration, learning and memory, and their brains were analyzed by immunohistochemistry (IHC) for vascularization and A(3 plaques. MSC-VEGF treatment favored the neovascularization and diminished senile plaques in hippocampal specific layers. Consequently, the treatment was able to provide behavioral benefits and reduce cognitive deficits by recovering the innate interest to novelty and counteracting memory deficits present in these AD transgenic animals. Therefore, this study has important therapeutic implications for the vascular damage in the neurodegeneration promoted by AD.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Depto Fisiol, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, Depto Fisiol, São Paulo, BrazilWeb of Science15engFrontiers Research FoundationFrontiers in Aging NeuroscienceAlzheimer's diseasememory deficitsmesenchymal stem cellvascular endothelial growth factorangiogenesisamyloid plaguesTherapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's diseaseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000332605400001.pdfapplication/pdf2568504${dspace.ui.url}/bitstream/11600/37546/1/WOS000332605400001.pdf7d021e7d84738cd8f4e920518b35af71MD51open accessTEXTWOS000332605400001.pdf.txtWOS000332605400001.pdf.txtExtracted texttext/plain68280${dspace.ui.url}/bitstream/11600/37546/2/WOS000332605400001.pdf.txte90ac48c0d56f20577a5fbdebc933446MD52open access11600/375462022-11-04 14:18:43.525open accessoai:repositorio.unifesp.br:11600/37546Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-11-04T17:18:43Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease |
title |
Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease |
spellingShingle |
Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease Garcia, Karina de Oliveira [UNIFESP] Alzheimer's disease memory deficits mesenchymal stem cell vascular endothelial growth factor angiogenesis amyloid plagues |
title_short |
Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease |
title_full |
Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease |
title_fullStr |
Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease |
title_full_unstemmed |
Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease |
title_sort |
Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease |
author |
Garcia, Karina de Oliveira [UNIFESP] |
author_facet |
Garcia, Karina de Oliveira [UNIFESP] Ornellas, Felipe Leite de Moraes [UNIFESP] Martin, Priscila Keiko Matsumoto [UNIFESP] Patti, Camilla L. [UNIFESP] Mello, Luiz Eugenio Araujo de Moraes [UNIFESP] Frussa-Filho, Roberto [UNIFESP] Han, Sang Won [UNIFESP] Longo, Beatriz Monteiro [UNIFESP] |
author_role |
author |
author2 |
Ornellas, Felipe Leite de Moraes [UNIFESP] Martin, Priscila Keiko Matsumoto [UNIFESP] Patti, Camilla L. [UNIFESP] Mello, Luiz Eugenio Araujo de Moraes [UNIFESP] Frussa-Filho, Roberto [UNIFESP] Han, Sang Won [UNIFESP] Longo, Beatriz Monteiro [UNIFESP] |
author2_role |
author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Garcia, Karina de Oliveira [UNIFESP] Ornellas, Felipe Leite de Moraes [UNIFESP] Martin, Priscila Keiko Matsumoto [UNIFESP] Patti, Camilla L. [UNIFESP] Mello, Luiz Eugenio Araujo de Moraes [UNIFESP] Frussa-Filho, Roberto [UNIFESP] Han, Sang Won [UNIFESP] Longo, Beatriz Monteiro [UNIFESP] |
dc.subject.eng.fl_str_mv |
Alzheimer's disease memory deficits mesenchymal stem cell vascular endothelial growth factor angiogenesis amyloid plagues |
topic |
Alzheimer's disease memory deficits mesenchymal stem cell vascular endothelial growth factor angiogenesis amyloid plagues |
description |
Alzheimer's disease (AD) is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits, such as alterations in social interactions. the major pathological features of AD are the formation of senile plaques and neurofibrillary tangles together with neuronal and vascular damage. the double transgenic mouse model of AD (2xTg-AD) with the APPswe/PS1dE9 mutations shows characteristics that are similar to those observed in AD patients, including social memory impairment, senile plaque formation and vascular deficits. Mesenchymal stem cells (MSCs), when transplanted into the brain, produce positive effects by reducing amyloid-beta (AN deposition in transgenic amyloid precursor protein (APP)/presenilins1 (PS1) mice. Vascular endothelial growth factor (VEGF), exhibits neuroprotective effects against the excitotoxicity implicated in the AD neurodegeneration. the present study investigates the effects of MSCs overexpressing VEGF in hippocampal neovascularization, cognitive dysfunction and senile plaques present in 2xTg-AD transgenic mice. MSC were transfected with vascular endothelial growth factor cloned in uP vector under control of modified CMV promoter (uP-VEGF) vector, by electroporation and expanded at the 14th passage. 2xTg-AD animals at 6, 9 and 12 months old were transplanted with MSC-VEGF or MSC. the animals were tested for behavioral tasks to access locomotion, novelty exploration, learning and memory, and their brains were analyzed by immunohistochemistry (IHC) for vascularization and A(3 plaques. MSC-VEGF treatment favored the neovascularization and diminished senile plaques in hippocampal specific layers. Consequently, the treatment was able to provide behavioral benefits and reduce cognitive deficits by recovering the innate interest to novelty and counteracting memory deficits present in these AD transgenic animals. Therefore, this study has important therapeutic implications for the vascular damage in the neurodegeneration promoted by AD. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-03-07 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:35:26Z |
dc.date.available.fl_str_mv |
2016-01-24T14:35:26Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Frontiers in Aging Neuroscience. Lausanne: Frontiers Research Foundation, v. 6, 15 p., 2014. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/37546 http://dx.doi.org/10.3389/fnagi.2014.00030 |
dc.identifier.issn.none.fl_str_mv |
1663-4365 |
dc.identifier.file.none.fl_str_mv |
WOS000332605400001.pdf |
dc.identifier.doi.none.fl_str_mv |
10.3389/fnagi.2014.00030 |
dc.identifier.wos.none.fl_str_mv |
WOS:000332605400001 |
identifier_str_mv |
Frontiers in Aging Neuroscience. Lausanne: Frontiers Research Foundation, v. 6, 15 p., 2014. 1663-4365 WOS000332605400001.pdf 10.3389/fnagi.2014.00030 WOS:000332605400001 |
url |
http://repositorio.unifesp.br/handle/11600/37546 http://dx.doi.org/10.3389/fnagi.2014.00030 |
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eng |
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Frontiers in Aging Neuroscience |
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Frontiers Research Foundation |
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Frontiers Research Foundation |
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