PMID- 19625522
OWN - NLM
STAT- MEDLINE
DCOM- 20090810
LR  - 20211028
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 29
IP  - 29
DP  - 2009 Jul 22
TI  - Decreased brain-derived neurotrophic factor depends on amyloid aggregation state 
      in transgenic mouse models of Alzheimer's disease.
PG  - 9321-9
LID - 10.1523/JNEUROSCI.4736-08.2009 [doi]
AB  - Downregulation of brain-derived neurotrophic factor (BDNF) in the cortex occurs 
      early in the progression of Alzheimer's disease (AD). Since BDNF plays a critical 
      role in neuronal survival, synaptic plasticity, and memory, BDNF reduction may 
      contribute to synaptic and cellular loss and memory deficits characteristic of 
      AD. In vitro evidence suggests that amyloid-beta (A beta) contributes to BDNF 
      downregulation in AD, but the specific A beta aggregation state responsible for 
      this downregulation in vivo is unknown. In the present study, we examined 
      cortical levels of BDNF mRNA in three different transgenic AD mouse models 
      harboring mutations in APP resulting in A beta overproduction, and in a genetic 
      mouse model of Down syndrome. Two of the three A beta transgenic strains 
      (APP(NLh) and TgCRND8) exhibited significantly decreased cortical BDNF mRNA 
      levels compared with wild-type mice, whereas neither the other strain 
      (APP(swe)/PS-1) nor the Down syndrome mouse model (Ts65Dn) was affected. Only 
      APP(NLh) and TgCRND8 mice expressed high A beta(42)/A beta(40) ratios and larger 
      SDS-stable A beta oligomers (approximately 115 kDa). TgCRND8 mice exhibited 
      downregulation of BDNF transcripts III and IV; transcript IV is also 
      downregulated in AD. Furthermore, in all transgenic mouse strains, there was a 
      correlation between levels of large oligomers, A beta(42)/A beta(40), and 
      severity of BDNF decrease. These data show that the amount and species of A beta 
      vary among transgenic mouse models of AD and are negatively correlated with BDNF 
      levels. These findings also suggest that the effect of A beta on decreased BDNF 
      expression is specific to the aggregation state of A beta and is dependent on 
      large oligomers.
FAU - Peng, Shiyong
AU  - Peng S
AD  - Department of Psychiatry and Behavioural Neurosciences, McMaster University, 
      Hamilton, Ontario L8N 3Z5, Canada.
FAU - Garzon, Diego J
AU  - Garzon DJ
FAU - Marchese, Monica
AU  - Marchese M
FAU - Klein, William
AU  - Klein W
FAU - Ginsberg, Stephen D
AU  - Ginsberg SD
FAU - Francis, Beverly M
AU  - Francis BM
FAU - Mount, Howard T J
AU  - Mount HT
FAU - Mufson, Elliott J
AU  - Mufson EJ
FAU - Salehi, Ahmad
AU  - Salehi A
FAU - Fahnestock, Margaret
AU  - Fahnestock M
LA  - eng
GR  - R01 AG043375/AG/NIA NIH HHS/United States
GR  - P01 AG014449/AG/NIA NIH HHS/United States
GR  - P01 NS048447/NS/NINDS NIH HHS/United States
GR  - R01 NS043939/NS/NINDS NIH HHS/United States
GR  - AG10688/AG/NIA NIH HHS/United States
GR  - P01 AG017617/AG/NIA NIH HHS/United States
GR  - 85042/CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (APP protein, human)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Presenilin-1)
RN  - 0 (Protease Nexins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Analysis of Variance
MH  - Animals
MH  - Blotting, Western
MH  - Brain/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Disease Models, Animal
MH  - Down Syndrome/genetics/metabolism
MH  - Down-Regulation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Polymerase Chain Reaction
MH  - Presenilin-1/genetics
MH  - Protease Nexins
MH  - RNA, Messenger/metabolism
MH  - Receptors, Cell Surface/genetics
PMC - PMC3411546
MID - CAMS2275
OID - NLM: CAMS2275
EDAT- 2009/07/25 09:00
MHDA- 2009/08/11 09:00
PMCR- 2010/01/22
CRDT- 2009/07/24 09:00
PHST- 2009/07/24 09:00 [entrez]
PHST- 2009/07/25 09:00 [pubmed]
PHST- 2009/08/11 09:00 [medline]
PHST- 2010/01/22 00:00 [pmc-release]
AID - 29/29/9321 [pii]
AID - 3497653 [pii]
AID - 10.1523/JNEUROSCI.4736-08.2009 [doi]
PST - ppublish
SO  - J Neurosci. 2009 Jul 22;29(29):9321-9. doi: 10.1523/JNEUROSCI.4736-08.2009.