PMID- 30586546
OWN - NLM
STAT- MEDLINE
DCOM- 20200625
LR  - 20200625
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1710
DP  - 2019 May 1
TI  - Brain-derived neurotrophic factor modified human umbilical cord mesenchymal stem 
      cells-derived cholinergic-like neurons improve spatial learning and memory 
      ability in Alzheimer's disease rats.
PG  - 61-73
LID - S0006-8993(18)30660-7 [pii]
LID - 10.1016/j.brainres.2018.12.034 [doi]
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disease and the most 
      common type of dementia. Although it is still incurable, stem cell replacement 
      therapy provides new hope for AD. Human umbilical cord mesenchymal stem cells 
      (hUC-MSCs) have multiple differentiation potentials, which can differentiate into 
      cholinergic-like neurons and promote the release of acetylcholine. Brain-derived 
      neurotrophic factor (BDNF) can also promote neurogenesis and synaptic formation, 
      reduce oxidative stress and cell death. Therefore, we investigated the 
      therapeutic effects of BDNF modified hUC-MSCs-derived cholinergic-like neurons in 
      AD rats in this study. To make AD models, 1 mul beta amyloid (Abeta)(1-42) was 
      injected into the right hippocampus of the rats. After two weeks, the 
      hUC-MSCs-derived cholinergic-like neurons null cells or overexpressing BDNF cells 
      delivered by lentiviralvectors were slowly injected into the right hippocampus of 
      the AD rats. After 8 weeks of transplantation, Morris water maze test, Western 
      blotting, Immunohistochemistry, Immunofluorescence assay and TdT mediated dUTP 
      Nick End Labeling (TUNEL) detection were performed. Transplantation of BDNF 
      modified hUC-MSCs-derived cholinergic-like neurons significantly improved spatial 
      learning and memory abilities in the AD rats, increased the release of 
      acetylcholine and ChAT expression in the hippocampus, enhanced the activation of 
      astrocytes and microglia, reduced the expression of Abeta and recombinant human 
      beta-site APP-cleaving enzyme1 (BACE1), inhibited neuronal apoptosis, and 
      promoted neurogenesis. Our results demonstrate that BDNF modified 
      hUC-MSCs-derived cholinergic-like neurons might be a promising therapeutic 
      strategy for AD.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Hu, Weiwei
AU  - Hu W
AD  - Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, Jiangsu 210011, China.
FAU - Feng, Zehua
AU  - Feng Z
AD  - School of Stomatology, Nanjing Medical University, Nanjing, Jiangsu 211166, 
      China.
FAU - Xu, Jun
AU  - Xu J
AD  - Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, Jiangsu 210011, China.
FAU - Jiang, Zhi
AU  - Jiang Z
AD  - Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, Jiangsu 210011, China.
FAU - Feng, Meijiang
AU  - Feng M
AD  - Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, Jiangsu 210011, China; Key Laboratory for Aging & Disease, 
      Nanjing Medical University, Nanjing, Jiangsu 210011, China. Electronic address: 
      mjfeng416@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181223
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/metabolism
MH  - Alzheimer Disease/*physiopathology/psychology
MH  - Amyloid beta-Peptides/metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*physiology
MH  - Cell Differentiation
MH  - Cholinergic Neurons/*physiology
MH  - Disease Models, Animal
MH  - Fetal Blood/cytology
MH  - Hippocampus/physiology
MH  - Humans
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*physiology
MH  - Rats, Sprague-Dawley
MH  - Spatial Learning/*physiology
MH  - Spatial Memory/*physiology
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Brain-derived neurotrophic factor
OT  - Cholinergic-like neuron
OT  - Human umbilical cord mesenchymal stem cell
EDAT- 2018/12/27 06:00
MHDA- 2020/06/26 06:00
CRDT- 2018/12/27 06:00
PHST- 2018/09/02 00:00 [received]
PHST- 2018/12/18 00:00 [revised]
PHST- 2018/12/21 00:00 [accepted]
PHST- 2018/12/27 06:00 [pubmed]
PHST- 2020/06/26 06:00 [medline]
PHST- 2018/12/27 06:00 [entrez]
AID - S0006-8993(18)30660-7 [pii]
AID - 10.1016/j.brainres.2018.12.034 [doi]
PST - ppublish
SO  - Brain Res. 2019 May 1;1710:61-73. doi: 10.1016/j.brainres.2018.12.034. Epub 2018 
      Dec 23.