PMID- 17760871
OWN - NLM
STAT- MEDLINE
DCOM- 20071213
LR  - 20220225
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 103
IP  - 4
DP  - 2007 Nov
TI  - Evidence of Abeta- and transgene-dependent defects in ERK-CREB signaling in 
      Alzheimer's models.
PG  - 1594-607
AB  - Extracellular-signal regulated kinase (ERK) signaling is critical for memory and 
      tightly regulated by acute environmental stimuli. In Alzheimer disease transgenic 
      models, active ERK is shown to first be increased, then later reduced, but 
      whether these baseline changes reflect disruptions in ERK signaling is less 
      clear. We investigated the influence of the familial Alzheimer's disease 
      transgene APPsw and beta-amyloid peptide (Abeta) immunoneutralization on 
      cannulation injury-associated (i.c.v. infusion) ERK activation. At both 12 and 22 
      months of age, the trauma-associated activation of ERK observed in Tg(-) mice was 
      dramatically attenuated in Tg(+). In cortices of 22-month-old non-infused mice, a 
      reduction in ERK activation was observed in Tg(+), relative to Tg(-) mice. 
      Intracerebroventricular (i.c.v.) anti-Abeta infusion significantly increased 
      phosphorylated ERK, its substrate cAMP-response element-binding protein (CREB) 
      and a downstream target, the NMDA receptor subunit. We also demonstrated that 
      Abeta oligomer decreased active ERK and subsequently active CREB in human 
      neuroblastoma cells, which could be prevented by oligomer immunoneutralization. 
      Abeta oligomers also inhibited active ERK and CREB in primary neurons, in 
      addition to reducing the downstream post-synaptic protein NMDA receptor subunit. 
      These effects were reversed by anti-oligomer. Our data strongly support the 
      existence of an APPsw transgene-dependent and Abeta oligomer-mediated defect in 
      regulation of ERK activation.
FAU - Ma, Qiu-Lan
AU  - Ma QL
AD  - Department of Medicine, University of California, Los Angeles, California, USA.
FAU - Harris-White, Marni E
AU  - Harris-White ME
FAU - Ubeda, Oliver J
AU  - Ubeda OJ
FAU - Simmons, Mychica
AU  - Simmons M
FAU - Beech, Walter
AU  - Beech W
FAU - Lim, Giselle P
AU  - Lim GP
FAU - Teter, Bruce
AU  - Teter B
FAU - Frautschy, Sally A
AU  - Frautschy SA
FAU - Cole, Greg M
AU  - Cole GM
LA  - eng
GR  - R01 AG021975-03/AG/NIA NIH HHS/United States
GR  - R01 NS043946-01/NS/NINDS NIH HHS/United States
GR  - R01 AG010685-10/AG/NIA NIH HHS/United States
GR  - R01 NS043946-05/NS/NINDS NIH HHS/United States
GR  - R01 NS043946/NS/NINDS NIH HHS/United States
GR  - R01 AG021975-04/AG/NIA NIH HHS/United States
GR  - R01 AG016793-05/AG/NIA NIH HHS/United States
GR  - R01 AG022080/AG/NIA NIH HHS/United States
GR  - R01 AG016793/AG/NIA NIH HHS/United States
GR  - R01 NS043946-04/NS/NINDS NIH HHS/United States
GR  - NS43946/NS/NINDS NIH HHS/United States
GR  - R01 AG016793-04/AG/NIA NIH HHS/United States
GR  - R01 AG010685-09/AG/NIA NIH HHS/United States
GR  - AG022080/AG/NIA NIH HHS/United States
GR  - R01 NS043946-03/NS/NINDS NIH HHS/United States
GR  - R01 AG010685-13/AG/NIA NIH HHS/United States
GR  - AG021975/AG/NIA NIH HHS/United States
GR  - R01 AG010685/AG/NIA NIH HHS/United States
GR  - R01 AG010685-12/AG/NIA NIH HHS/United States
GR  - R01 AG010685-11/AG/NIA NIH HHS/United States
GR  - R01 AG016793-03/AG/NIA NIH HHS/United States
GR  - R01 AG021975-02/AG/NIA NIH HHS/United States
GR  - R01 NS043946-02/NS/NINDS NIH HHS/United States
GR  - R01 AG021975-01A2/AG/NIA NIH HHS/United States
GR  - R01 AG010685-14/AG/NIA NIH HHS/United States
GR  - R01 AG021975/AG/NIA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070830
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Amyloid beta-Peptides)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.3.1.48 (Crebbp protein, mouse)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Alzheimer Disease/*enzymology/genetics/metabolism
MH  - Amyloid beta-Peptides/genetics/*physiology
MH  - Animals
MH  - CREB-Binding Protein/genetics/*physiology
MH  - Cell Line, Tumor
MH  - Disease Models, Animal
MH  - Enzyme Activation/genetics
MH  - Extracellular Signal-Regulated MAP Kinases/genetics/*physiology
MH  - Humans
MH  - MAP Kinase Signaling System/*genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Transgenes/*physiology
PMC - PMC2527620
MID - NIHMS57160
EDAT- 2007/09/01 09:00
MHDA- 2007/12/14 09:00
PMCR- 2008/09/01
CRDT- 2007/09/01 09:00
PHST- 2007/09/01 09:00 [pubmed]
PHST- 2007/12/14 09:00 [medline]
PHST- 2007/09/01 09:00 [entrez]
PHST- 2008/09/01 00:00 [pmc-release]
AID - JNC4869 [pii]
AID - 10.1111/j.1471-4159.2007.04869.x [doi]
PST - ppublish
SO  - J Neurochem. 2007 Nov;103(4):1594-607. doi: 10.1111/j.1471-4159.2007.04869.x. 
      Epub 2007 Aug 30.