PMID- 19540623
OWN - NLM
STAT- MEDLINE
DCOM- 20110817
LR  - 20211020
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Print)
IS  - 0197-4580 (Linking)
VI  - 32
IP  - 5
DP  - 2011 May
TI  - beta-Amyloid impairs axonal BDNF retrograde trafficking.
PG  - 821-33
LID - 10.1016/j.neurobiolaging.2009.05.012 [doi]
AB  - The neurotrophin, brain-derived neurotrophic factor (BDNF), is essential for 
      synaptic function, plasticity and neuronal survival. At the axon terminal, when 
      BDNF binds to its receptor, tropomyosin-related kinase B (TrkB), the signal is 
      propagated along the axon to the cell body, via retrograde transport, regulating 
      gene expression and neuronal function. Alzheimer disease (AD) is characterized by 
      early impairments in synaptic function that may result in part from neurotrophin 
      signaling deficits. Growing evidence suggests that soluble beta-amyloid (Abeta) 
      assemblies cause synaptic dysfunction by disrupting both neurotransmitter and 
      neurotrophin signaling. Utilizing a novel microfluidic culture chamber, we 
      demonstrate a BDNF retrograde signaling deficit in AD transgenic mouse neurons 
      (Tg2576) that can be reversed by gamma-secretase inhibitors. Using BDNF-GFP, we show 
      that BDNF-mediated TrkB retrograde trafficking is impaired in Tg2576 axons. 
      Furthermore, Abeta oligomers alone impair BDNF retrograde transport. Thus, Abeta 
      reduces BDNF signaling by impairing axonal transport and this may underlie the 
      synaptic dysfunction observed in AD.
CI  - Published by Elsevier Inc.
FAU - Poon, Wayne W
AU  - Poon WW
AD  - Institute for Brain Aging and Dementia, University of California, Irvine, 1226 
      Gillespie NRF, Irvine, CA 92697, United States. wpoon@uci.edu
FAU - Blurton-Jones, Mathew
AU  - Blurton-Jones M
FAU - Tu, Christina H
AU  - Tu CH
FAU - Feinberg, Leila M
AU  - Feinberg LM
FAU - Chabrier, Meredith A
AU  - Chabrier MA
FAU - Harris, Joe W
AU  - Harris JW
FAU - Jeon, Noo Li
AU  - Jeon NL
FAU - Cotman, Carl W
AU  - Cotman CW
LA  - eng
GR  - T32 AG000096-29/AG/NIA NIH HHS/United States
GR  - AG029378/AG/NIA NIH HHS/United States
GR  - P01 AG000538/AG/NIA NIH HHS/United States
GR  - P50 AG016573-01A1/AG/NIA NIH HHS/United States
GR  - K01 AG029378-03/AG/NIA NIH HHS/United States
GR  - AG016573/AG/NIA NIH HHS/United States
GR  - P50 AG016573/AG/NIA NIH HHS/United States
GR  - K01 AG029378/AG/NIA NIH HHS/United States
GR  - P50 AG016573-12/AG/NIA NIH HHS/United States
GR  - AG00538/AG/NIA NIH HHS/United States
GR  - T32 AG000096/AG/NIA NIH HHS/United States
GR  - AG000096/AG/NIA NIH HHS/United States
GR  - K01 AG029378-02/AG/NIA NIH HHS/United States
GR  - K01 AG029378-01A2/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090621
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
SB  - IM
MH  - Alzheimer Disease/drug therapy/*metabolism
MH  - Amyloid Precursor Protein Secretases/antagonists & inhibitors
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Axonal Transport/drug effects/*physiology
MH  - Axons/drug effects/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Culture Techniques
MH  - Mice
MH  - Mice, Transgenic
MH  - Microfluidics
MH  - Protein Transport
MH  - Receptor, trkB/metabolism
PMC - PMC3038182
MID - NIHMS244888
EDAT- 2009/06/23 09:00
MHDA- 2011/08/19 06:00
PMCR- 2012/05/01
CRDT- 2009/06/23 09:00
PHST- 2008/06/26 00:00 [received]
PHST- 2009/05/07 00:00 [revised]
PHST- 2009/05/08 00:00 [accepted]
PHST- 2009/06/23 09:00 [entrez]
PHST- 2009/06/23 09:00 [pubmed]
PHST- 2011/08/19 06:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - S0197-4580(09)00168-7 [pii]
AID - 10.1016/j.neurobiolaging.2009.05.012 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2011 May;32(5):821-33. doi: 
      10.1016/j.neurobiolaging.2009.05.012. Epub 2009 Jun 21.