title: Amniotic Mesenchymal Stem Cells Decrease Aβ Deposition and Improve Memory in APP/PS1 Transgenic Mice.
abstract: Transplantation of human amniotic mesenchymal stem cells (hAM-MSCs) seems to be a promising strategy for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, the clinical therapeutic effects of hAM-MSCs and their mechanisms of action in AD remain to be determined. Here, we used amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice to evaluate the effects of hAM-MSC transplantation on AD-related neuropathology and cognitive dysfunction. We found that hAM-MSC transplantation into the hippocampus dramatically reduced amyloid-β peptide (Aβ) deposition and rescued spatial learning and memory deficits in APP/PS1 mice. Interestingly, these effects were associated with increasing in Aβ-degrading factors, elevations in activated microglia, and the modulation of neuroinflammation. Furthermore, enhanced hippocampal neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG) and enhanced synaptic plasticity following hAM-MSC treatment could be another important factor in reversing the cognitive decline in APP/PS1 mice. Instead, the mechanism underlying the improved cognition apparently involves a robust increase in hippocampal synaptic density and neurogenesis that is mediated by brain-derived neurotrophic factor (BDNF). In conclusion, our data suggest that hAM-MSCs may be a new and effective therapy for the treatment of AD.
authors.affiliation: Department of Intensive-Care Unit, Affiliated First Hospital, Jinan University, Guangzhou, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, Affiliated First Hospital, Jinan University, Region, No. 613, Huangpudadaoxi, Tianhe District, Guangzhou, 510630, China.
authors.forename: Qian-Quan
authors.initials: QQ
authors.lastname: Wan
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Chuan-Yi
authors.initials: CY
authors.lastname: Zheng
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Hong-Long
authors.initials: HL
authors.lastname: Zhou
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Xing-Yu
authors.initials: XY
authors.lastname: Dong
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Deng
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Mou
authors.initials: M
authors.lastname: Gao
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Zhong-Jie
authors.initials: ZJ
authors.lastname: Yan
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: You
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Neurosurgery, Affiliated First Hospital, Jinan University, Region, No. 613, Huangpudadaoxi, Tianhe District, Guangzhou, 510630, China. wang_xy123@126.com.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Affiliated First Hospital, Jinan University, Region, No. 613, Huangpudadaoxi, Tianhe District, Guangzhou, 510630, China. tcken@jun.edu.cn.
authors.forename: Ke-En
authors.initials: KE
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Affiliated First Hospital, Jinan University, Region, No. 613, Huangpudadaoxi, Tianhe District, Guangzhou, 510630, China. zmaoying2009@163.com.
authors.forename: Mao-Ying
authors.initials: MY
authors.lastname: Zhang
authors.affiliation: Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, China. xuruxiangbrain@163.com.
authors.forename: Ru-Xiang
authors.initials: RX
authors.lastname: Xu
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods / Q000639:trends*; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1
keywords: Alzheimer’s disease; BDNF; Neurogenesis; Neuroinflammation; Synaptic plasticity; hAM-MSCs