Research Paper Volume 13, Issue 14 pp 18131—18149
Grape skin extract modulates neuronal stem cell proliferation and improves spatial learning in senescence-accelerated prone 8 mice
- 1 Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan
- 2 Open Innovation Laboratory for Food and Medicinal Resource Engineering, National Institute of Advanced Industrial Science and Technology (AIST) and University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan
- 3 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK
- 4 Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan
Received: May 18, 2021 Accepted: July 15, 2021 Published: July 28, 2021
https://doi.org/10.18632/aging.203373How to Cite
Copyright: © 2021 Sasaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
In recent years, the number of patients with neurodegenerative illness such as Alzheimer’s disease (AD) has increased with the aging of the population. In this study, we evaluated the effect of Grape skin extract (GSE) on neurotypic SH-SY5Y cells as an in vitro AD model, murine neurospheres as an ex vivo neurogenesis model and SAMP8 mice as an in vivo AD model. Our in vitro result showed that pre-treatment of SH-SY5Y cells with GSE ameliorated Aβ-induced cytotoxicity. Moreover, GSE treatment significantly decreased the number of neurospheres, but increased their size suggesting reduced stem cell self-renewal but increased proliferation. Our in vivo Morris water maze test indicated that GSE improves learning and memory in SAMP8 mice. To detect proliferation and newborn neurons, we measured BrdU+ cells in the dentate gyrus (DG). GSE treatment increased the number of BrdU+ cells in the DG of SAMP8 mice. Finally, we showed that GSE induced a decrease in inflammatory cytokines and an increase in neurotransmitters in the cerebral cortex of SAMP8 mice. These results suggested that GSE increased neurogenic zone proliferation and memory but decreased oxidative stress associated with pro-inflammatory cytokines in aging, thus protecting neurons.