Mesenchymal Stem Cells Therapy Improved the Streptozotocin-Induced Behavioral and Hippocampal Impairment in Rats

Sporadic Alzheimer’s disease (sAD) is the most prevalent neurodegenerative pathology with no effective therapy until date. This disease promotes hippocampal degeneration, which in turn affects multiple cognitive domains and daily life activities. In this study, we hypothesized that long-lasting ther...

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Autores principales: Zappa Villar, María Florencia, López Hanotte, Juliette, Pardo, Joaquín, Morel, Gustavo Ramón, Mazzolini, Guillermo, García, Mariana, Reggiani, Paula Cecilia
Formato: Articulo
Lenguaje:Inglés
Publicado: 2019
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/124052
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id I19-R120-10915-124052
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Cognitive function
Mesenchymal stem cell
Microglía
Sporadic Alzheimer’s disease
Synaptic proteins
spellingShingle Ciencias Médicas
Cognitive function
Mesenchymal stem cell
Microglía
Sporadic Alzheimer’s disease
Synaptic proteins
Zappa Villar, María Florencia
López Hanotte, Juliette
Pardo, Joaquín
Morel, Gustavo Ramón
Mazzolini, Guillermo
García, Mariana
Reggiani, Paula Cecilia
Mesenchymal Stem Cells Therapy Improved the Streptozotocin-Induced Behavioral and Hippocampal Impairment in Rats
topic_facet Ciencias Médicas
Cognitive function
Mesenchymal stem cell
Microglía
Sporadic Alzheimer’s disease
Synaptic proteins
description Sporadic Alzheimer’s disease (sAD) is the most prevalent neurodegenerative pathology with no effective therapy until date. This disease promotes hippocampal degeneration, which in turn affects multiple cognitive domains and daily life activities. In this study, we hypothesized that long-lasting therapy with mesenchymal stem cells (MSC) would have a restorative effect on the behavioral alterations and cognitive decline typical of sAD, as they have shown neurogenic and immunomodulatory activities. To test this, we chronically injected intravenous human MSC in a sAD rat model induced by the intracerebroventricular injection of streptozotocin (STZ). During the last 2 weeks, we performed open field, Barnes maze, and marble burying tests. STZ-treated rats displayed a poor performance in all behavioral tests. Cell therapy increased exploratory behavior, decreased anxiety, and improved spatial memory and marble burying behavior, the latter being representative of daily life activities. On the hippocampus, we found that STZ promotes neuronal loss in the <i>Cornus Ammoni</i> (CA1) field and decreased neurogenesis in the dentate gyrus. Also, STZ induced a reduction in hippocampal volume and presynaptic protein levels and an exacerbated microgliosis, relevant AD features. The therapy rescued CA1 neurodegeneration but did not reverse the decrease of immature neurons, suggesting that the therapy effect varied among hippocampal neuronal populations. Importantly, cell therapy ameliorated microgliosis and restored hippocampal atrophy and some presynaptic protein levels in the sAD model. These findings, by showing that intravenous injection of human MSC restores behavioral and hippocampal alterations in experimental sAD, support the potential use of MSC therapy for the treatment of neurodegenerative diseases.
format Articulo
Articulo
author Zappa Villar, María Florencia
López Hanotte, Juliette
Pardo, Joaquín
Morel, Gustavo Ramón
Mazzolini, Guillermo
García, Mariana
Reggiani, Paula Cecilia
author_facet Zappa Villar, María Florencia
López Hanotte, Juliette
Pardo, Joaquín
Morel, Gustavo Ramón
Mazzolini, Guillermo
García, Mariana
Reggiani, Paula Cecilia
author_sort Zappa Villar, María Florencia
title Mesenchymal Stem Cells Therapy Improved the Streptozotocin-Induced Behavioral and Hippocampal Impairment in Rats
title_short Mesenchymal Stem Cells Therapy Improved the Streptozotocin-Induced Behavioral and Hippocampal Impairment in Rats
title_full Mesenchymal Stem Cells Therapy Improved the Streptozotocin-Induced Behavioral and Hippocampal Impairment in Rats
title_fullStr Mesenchymal Stem Cells Therapy Improved the Streptozotocin-Induced Behavioral and Hippocampal Impairment in Rats
title_full_unstemmed Mesenchymal Stem Cells Therapy Improved the Streptozotocin-Induced Behavioral and Hippocampal Impairment in Rats
title_sort mesenchymal stem cells therapy improved the streptozotocin-induced behavioral and hippocampal impairment in rats
publishDate 2019
url http://sedici.unlp.edu.ar/handle/10915/124052
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