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Int. J. Mol. Sci. 2016, 17(2), 152; doi:10.3390/ijms17020152

Mesenchymal Stem Cells Preserve Working Memory in the 3xTg-AD Mouse Model of Alzheimer’s Disease

1
Department of Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic
2
Department of Neuroscience, 2nd Faculty of Medicine, Charles University, Prague 150 06, Czech Republic
3
Functional Neuroanatomy Laboratory, Department of Neuroscience, Faculty of Medicine, the University of the Basque Country, 48940 Leioa, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Wilhelm Bloch
Received: 2 November 2015 / Revised: 12 January 2016 / Accepted: 20 January 2016 / Published: 25 January 2016
(This article belongs to the Special Issue Stem Cell Activation in Adult Organism)
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Abstract

The transplantation of stem cells may have a therapeutic effect on the pathogenesis and progression of neurodegenerative disorders. In the present study, we transplanted human mesenchymal stem cells (MSCs) into the lateral ventricle of a triple transgenic mouse model of Alzheimer´s disease (3xTg-AD) at the age of eight months. We evaluated spatial reference and working memory after MSC treatment and the possible underlying mechanisms, such as the influence of transplanted MSCs on neurogenesis in the subventricular zone (SVZ) and the expression levels of a 56 kDa oligomer of amyloid β (Aβ*56), glutamine synthetase (GS) and glutamate transporters (Glutamate aspartate transporter (GLAST) and Glutamate transporter-1 (GLT-1)) in the entorhinal and prefrontal cortices and the hippocampus. At 14 months of age we observed the preservation of working memory in MSC-treated 3xTg-AD mice, suggesting that such preservation might be due to the protective effect of MSCs on GS levels and the considerable downregulation of Aβ*56 levels in the entorhinal cortex. These changes were observed six months after transplantation, accompanied by clusters of proliferating cells in the SVZ. Since the grafted cells did not survive for the whole experimental period, it is likely that the observed effects could have been transiently more pronounced at earlier time points than at six months after cell application. View Full-Text
Keywords: Alzheimer’s disease; mesenchymal stem cells; working memory; Aβ*56; neurogenesis Alzheimer’s disease; mesenchymal stem cells; working memory; Aβ*56; neurogenesis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ruzicka, J.; Kulijewicz-Nawrot, M.; Rodrigez-Arellano, J.J.; Jendelova, P.; Sykova, E. Mesenchymal Stem Cells Preserve Working Memory in the 3xTg-AD Mouse Model of Alzheimer’s Disease. Int. J. Mol. Sci. 2016, 17, 152.

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