PMID- 25526861
OWN - NLM
STAT- MEDLINE
DCOM- 20170301
LR  - 20191210
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 53
IP  - 3
DP  - 2016 Apr
TI  - Bone Marrow-Derived Endothelial Progenitor Cells Protect Against 
      Scopolamine-Induced Alzheimer-Like Pathological Aberrations.
PG  - 1403-1418
LID - 10.1007/s12035-014-9051-8 [doi]
AB  - Vascular endothelial dysfunction plays a key role in the pathogenesis of 
      Alzheimer's disease (AD). Patients with AD have displayed decreased circulating 
      endothelial progenitor cells (EPCs) which repair and maintain the endothelial 
      function. Transplantation of EPCs has emerged as a promising approach for the 
      management of cerebrovascular diseases including ischemic stroke, however, its 
      impact on AD has been poorly described. Thus, the current study aimed at 
      investigating the effects of bone marrow-derived (BM) EPCs transplantation in 
      repeated scopolamine-induced cognitive impairment, an experimental model that 
      replicates biomarkers of AD. Intravenously transplanted BM-EPCs migrated into the 
      brain of rats and improved the learning and memory deficits. Meanwhile, they 
      mitigated the deposition of amyloid plaques and associated histopathological 
      alterations. At the molecular levels, BM-EPCs blunted the increase of hippocampal 
      amyloid beta protein (Abeta), amyloid precursor protein (APP) and reinstated the 
      Abeta-degrading neprilysin together with downregulation of p-tau and its upstream 
      glycogen synthase kinase-3beta (GSK-3beta). They also corrected the perturbations of 
      neurotransmitter levels including restoration of acetylcholine and associated 
      esterase along with dopamine, GABA, and the neuroexitatory glutamate. 
      Furthermore, BM-EPCs induced behavioral recovery via boosting of vascular 
      endothelial growth factor (VEGF), nerve growth factor (NGF), brain-derived 
      neurotrophic factor (BDNF) and its upstream cAMP response element binding (CREB), 
      suppression of the proinflammatory tumor necrosis factor-alpha (TNF-alpha) and 
      interleukin-1beta (IL-1beta), and upregulation of interleukin-10 (IL-10). BM-EPCs also 
      augmented Nrf2 and seladin-1. Generally, these actions were analogous to those 
      exerted by adipose tissue-derived mesenchymal stem cells (AT-MSCs) and the 
      reference anti-Alzheimer donepezil. For the first time, these findings highlight 
      the beneficial actions of BM-EPCs against the memory deficits and AD-like 
      pathological dysfunction.
FAU - Safar, Marwa M
AU  - Safar MM
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, 
      Cairo, 11562, Egypt.
FAU - Arab, Hany H
AU  - Arab HH
AD  - Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, 
      Egypt. hany.arab@pharma.cu.edu.eg.
FAU - Rizk, Sherine M
AU  - Rizk SM
AD  - Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, 
      Egypt.
FAU - El-Maraghy, Shohda A
AU  - El-Maraghy SA
AD  - Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, 
      Egypt.
LA  - eng
PT  - Journal Article
DEP - 20141221
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Cytokines)
RN  - 0 (Indans)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Piperidines)
RN  - 8SSC91326P (Donepezil)
RN  - DL48G20X8X (Scopolamine)
SB  - IM
MH  - Adipose Tissue/cytology
MH  - Alzheimer Disease/chemically induced/pathology/*prevention & control
MH  - Animals
MH  - Cell Movement
MH  - Cells, Cultured
MH  - Cognition Disorders/chemically induced/therapy
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Donepezil
MH  - Endothelial Progenitor Cells/*transplantation
MH  - Gene Expression Profiling
MH  - Hippocampus/metabolism/pathology
MH  - Indans/therapeutic use
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Learning Disabilities/chemically induced/therapy
MH  - Male
MH  - Maze Learning
MH  - Mesenchymal Stem Cell Transplantation
MH  - Nerve Tissue Proteins/analysis
MH  - Neurotransmitter Agents/metabolism
MH  - Piperidines/therapeutic use
MH  - Random Allocation
MH  - Rats
MH  - Rats, Wistar
MH  - Scopolamine/toxicity
OTO - NOTNLM
OT  - Alzheimer
OT  - Amyloid beta-protein
OT  - Endothelial progenitor cells
OT  - Neuroinflammation
OT  - Neurotransmitters
OT  - Neurotrophic factors
EDAT- 2014/12/21 06:00
MHDA- 2017/03/03 06:00
CRDT- 2014/12/21 06:00
PHST- 2014/11/01 00:00 [received]
PHST- 2014/12/02 00:00 [accepted]
PHST- 2014/12/21 06:00 [entrez]
PHST- 2014/12/21 06:00 [pubmed]
PHST- 2017/03/03 06:00 [medline]
AID - 10.1007/s12035-014-9051-8 [pii]
AID - 10.1007/s12035-014-9051-8 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2016 Apr;53(3):1403-1418. doi: 10.1007/s12035-014-9051-8. Epub 
      2014 Dec 21.