Journal
JOURNAL OF NEUROCHEMISTRY
Volume 103, Issue 4, Pages 1594-1607Publisher
WILEY
DOI: 10.1111/j.1471-4159.2007.04869.x
Keywords
alzheimer disease; cAMP-response element-binding protein; extracellular-signal regulated kinase; immunization; signal transduction; Tg2576 mice
Categories
Funding
- NIA NIH HHS [R01 AG010685-13, R01 AG021975, R01 AG010685-14, R01 AG021975-01A2, AG021975, AG022080, R01 AG010685, R01 AG010685-12, R01 AG010685-09, R01 AG010685-11, R01 AG016793-04, R01 AG021975-02, R01 AG016793-03, R01 AG021975-03, R01 AG010685-10, R01 AG021975-04, R01 AG016793-05, R01 AG022080, R01 AG016793] Funding Source: Medline
- NINDS NIH HHS [R01 NS043946-05, NS43946, R01 NS043946-01, R01 NS043946-04, R01 NS043946-03, R01 NS043946, R01 NS043946-02] Funding Source: Medline
Ask authors/readers for more resources
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 (Ab) 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-Ab 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 Ab oligomer decreased active ERK and subsequently active CREB in human neuroblastoma cells, which could be prevented by oligomer immunoneutralization. Ab 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 Ab oligomer- mediated defect in regulation of ERK activation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available