PMID- 19198615
OWN - NLM
STAT- MEDLINE
DCOM- 20090330
LR  - 20220408
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 15
IP  - 3
DP  - 2009 Mar
TI  - Neuroprotective effects of brain-derived neurotrophic factor in rodent and 
      primate models of Alzheimer's disease.
PG  - 331-7
LID - 10.1038/nm.1912 [doi]
AB  - Profound neuronal dysfunction in the entorhinal cortex contributes to early loss 
      of short-term memory in Alzheimer's disease. Here we show broad neuroprotective 
      effects of entorhinal brain-derived neurotrophic factor (BDNF) administration in 
      several animal models of Alzheimer's disease, with extension of therapeutic 
      benefits into the degenerating hippocampus. In amyloid-transgenic mice, BDNF gene 
      delivery, when administered after disease onset, reverses synapse loss, partially 
      normalizes aberrant gene expression, improves cell signaling and restores 
      learning and memory. These outcomes occur independently of effects on amyloid 
      plaque load. In aged rats, BDNF infusion reverses cognitive decline, improves 
      age-related perturbations in gene expression and restores cell signaling. In 
      adult rats and primates, BDNF prevents lesion-induced death of entorhinal 
      cortical neurons. In aged primates, BDNF reverses neuronal atrophy and 
      ameliorates age-related cognitive impairment. Collectively, these findings 
      indicate that BDNF exerts substantial protective effects on crucial neuronal 
      circuitry involved in Alzheimer's disease, acting through amyloid-independent 
      mechanisms. BDNF therapeutic delivery merits exploration as a potential therapy 
      for Alzheimer's disease.
FAU - Nagahara, Alan H
AU  - Nagahara AH
AD  - Department of Neurosciences-0626, 9500 Gilman Drive, University of California-San 
      Diego, La Jolla, California 92093, USA.
FAU - Merrill, David A
AU  - Merrill DA
FAU - Coppola, Giovanni
AU  - Coppola G
FAU - Tsukada, Shingo
AU  - Tsukada S
FAU - Schroeder, Brock E
AU  - Schroeder BE
FAU - Shaked, Gideon M
AU  - Shaked GM
FAU - Wang, Ling
AU  - Wang L
FAU - Blesch, Armin
AU  - Blesch A
FAU - Kim, Albert
AU  - Kim A
FAU - Conner, James M
AU  - Conner JM
FAU - Rockenstein, Edward
AU  - Rockenstein E
FAU - Chao, Moses V
AU  - Chao MV
FAU - Koo, Edward H
AU  - Koo EH
FAU - Geschwind, Daniel
AU  - Geschwind D
FAU - Masliah, Eliezer
AU  - Masliah E
FAU - Chiba, Andrea A
AU  - Chiba AA
FAU - Tuszynski, Mark H
AU  - Tuszynski MH
LA  - eng
SI  - GEO/GSE14522
GR  - P01 AG010435-160006/AG/NIA NIH HHS/United States
GR  - R37 AG018440-09/AG/NIA NIH HHS/United States
GR  - P01 AG022074/AG/NIA NIH HHS/United States
GR  - P01 AG022074-050004/AG/NIA NIH HHS/United States
GR  - AG10435/AG/NIA NIH HHS/United States
GR  - P01 AG010435-160003/AG/NIA NIH HHS/United States
GR  - R37 AG018440/AG/NIA NIH HHS/United States
GR  - P01 AG010435/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090208
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
SB  - IM
CIN - Nat Rev Drug Discov. 2009 Apr;8(4):275. PMID: 19348027
MH  - Alzheimer Disease/*drug therapy
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*therapeutic use
MH  - *Disease Models, Animal
MH  - Mice
MH  - Mice, Transgenic
MH  - Neuroprotective Agents/*therapeutic use
MH  - Primates
PMC - PMC2838375
MID - NIHMS181778
EDAT- 2009/02/10 09:00
MHDA- 2009/03/31 09:00
PMCR- 2010/03/15
CRDT- 2009/02/10 09:00
PHST- 2008/07/17 00:00 [received]
PHST- 2008/12/23 00:00 [accepted]
PHST- 2009/02/10 09:00 [entrez]
PHST- 2009/02/10 09:00 [pubmed]
PHST- 2009/03/31 09:00 [medline]
PHST- 2010/03/15 00:00 [pmc-release]
AID - nm.1912 [pii]
AID - 10.1038/nm.1912 [doi]
PST - ppublish
SO  - Nat Med. 2009 Mar;15(3):331-7. doi: 10.1038/nm.1912. Epub 2009 Feb 8.