PMID- 19633196
OWN - NLM
STAT- MEDLINE
DCOM- 20090921
LR  - 20220309
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 32
DP  - 2009 Aug 11
TI  - Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer 
      disease.
PG  - 13594-9
LID - 10.1073/pnas.0901402106 [doi]
AB  - Neural stem cell (NSC) transplantation represents an unexplored approach for 
      treating neurodegenerative disorders associated with cognitive decline such as 
      Alzheimer disease (AD). Here, we used aged triple transgenic mice (3xTg-AD) that 
      express pathogenic forms of amyloid precursor protein, presenilin, and tau to 
      investigate the effect of neural stem cell transplantation on AD-related 
      neuropathology and cognitive dysfunction. Interestingly, despite widespread and 
      established Ass plaque and neurofibrillary tangle pathology, hippocampal neural 
      stem cell transplantation rescues the spatial learning and memory deficits in 
      aged 3xTg-AD mice. Remarkably, cognitive function is improved without altering 
      Ass or tau pathology. Instead, the mechanism underlying the improved cognition 
      involves a robust enhancement of hippocampal synaptic density, mediated by 
      brain-derived neurotrophic factor (BDNF). Gain-of-function studies show that 
      recombinant BDNF mimics the beneficial effects of NSC transplantation. 
      Furthermore, loss-of-function studies show that depletion of NSC-derived BDNF 
      fails to improve cognition or restore hippocampal synaptic density. Taken 
      together, our findings demonstrate that neural stem cells can ameliorate complex 
      behavioral deficits associated with widespread Alzheimer disease pathology via 
      BDNF.
FAU - Blurton-Jones, Mathew
AU  - Blurton-Jones M
AD  - Department of Neurobiology and Behavior and Institute for Memory Impairments and 
      Neurological Disorders, University of California, Irvine, CA 92697, USA.
FAU - Kitazawa, Masashi
AU  - Kitazawa M
FAU - Martinez-Coria, Hilda
AU  - Martinez-Coria H
FAU - Castello, Nicholas A
AU  - Castello NA
FAU - Muller, Franz-Josef
AU  - Muller FJ
FAU - Loring, Jeanne F
AU  - Loring JF
FAU - Yamasaki, Tritia R
AU  - Yamasaki TR
FAU - Poon, Wayne W
AU  - Poon WW
FAU - Green, Kim N
AU  - Green KN
FAU - LaFerla, Frank M
AU  - LaFerla FM
LA  - eng
GR  - P50 AG016573/AG/NIA NIH HHS/United States
GR  - K01 AG029378/AG/NIA NIH HHS/United States
GR  - P50AG16573/AG/NIA NIH HHS/United States
GR  - K01 AG029378-02/AG/NIA NIH HHS/United States
GR  - R01 AG027544/AG/NIA NIH HHS/United States
GR  - AG027544/AG/NIA NIH HHS/United States
GR  - K99AR05695/AR/NIAMS NIH HHS/United States
GR  - K01 AG029378-01A2/AG/NIA NIH HHS/United States
GR  - K01AG029378/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090724
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (tau Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Alzheimer Disease/*metabolism/*pathology
MH  - Animals
MH  - Astrocytes/cytology/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Chemotaxis
MH  - *Cognition
MH  - Cognition Disorders/pathology
MH  - Disease Models, Animal
MH  - Green Fluorescent Proteins/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Multipotent Stem Cells/cytology/metabolism
MH  - Neurons/*cytology/metabolism
MH  - Oligodendroglia/cytology/metabolism
MH  - Plaque, Amyloid/pathology
MH  - Stem Cell Transplantation
MH  - Stem Cells/*cytology/metabolism
MH  - Synapses/metabolism/pathology
MH  - tau Proteins/metabolism
PMC - PMC2715325
COIS- The authors declare no conflict of interest.
EDAT- 2009/07/28 09:00
MHDA- 2009/09/22 06:00
PMCR- 2009/07/24
CRDT- 2009/07/28 09:00
PHST- 2009/07/28 09:00 [entrez]
PHST- 2009/07/28 09:00 [pubmed]
PHST- 2009/09/22 06:00 [medline]
PHST- 2009/07/24 00:00 [pmc-release]
AID - 0901402106 [pii]
AID - 8972 [pii]
AID - 10.1073/pnas.0901402106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13594-9. doi: 
      10.1073/pnas.0901402106. Epub 2009 Jul 24.