PMID- 20122965
OWN - NLM
STAT- MEDLINE
DCOM- 20100525
LR  - 20191210
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 209
IP  - 1
DP  - 2010 May 1
TI  - The role of TNF-alpha signaling pathway on COX-2 upregulation and cognitive 
      decline induced by beta-amyloid peptide.
PG  - 165-73
LID - 10.1016/j.bbr.2010.01.040 [doi]
AB  - Alzheimer's disease (AD), a chronic degenerative and inflammatory brain disorder 
      characterized by neuronal dysfunction and loss, is linked to accumulation of 
      beta-amyloid (Abeta) peptide. Tumor necrosis factor-alpha (TNF-alpha) and 
      cyclooxygenase-2 (COX-2) are proteins that have key roles in immune cell 
      activation, inflammation and cognitive function in the brain. Here, we evaluated 
      the link between TNF-alpha and COX-2 on the acute responses elicited by Abeta. 
      Behavioral and molecular analyses were performed in mice after an 
      intracerebroventricular (i.c.v.) injection of Abeta(1-40). Genetic and/or 
      pharmacological approaches were used to inhibit TNF-alpha and COX-2. I.c.v. 
      Abeta(1-40) injection in mice activates TNF-alpha signaling pathway resulting in 
      COX-2 upregulation, synaptic loss and cognitive decline. Pharmacological studies 
      revealed that COX-2 is involved in the cognitive impairment mediated by 
      TNF-alpha. However, COX-2 inhibition failed in reducing the synaptophysin loss 
      induced by Abeta(1-40). The COX-2 upregulation induced by Abeta(1-40) was 
      attributed to activation of different protein kinases and transcriptional factors 
      that are greatly regulated by TNF-alpha. Together, these results indicate that 
      Abeta(1-40) induces the activation of several TNF-alpha-dependent intracellular 
      signaling pathways that play a key role in the control of COX-2 upregulation and 
      activation, synaptic loss and cognitive decline in mice. Therefore, selective 
      TNF-alpha inhibitors may be potentially interesting tools for AD drug 
      development.
FAU - Medeiros, Rodrigo
AU  - Medeiros R
AD  - Departamento de Farmacologia, Universidade Federal de Santa Catarina, Santa 
      Catarina, Brazil.
FAU - Figueiredo, Claudia P
AU  - Figueiredo CP
FAU - Pandolfo, Pablo
AU  - Pandolfo P
FAU - Duarte, Filipe S
AU  - Duarte FS
FAU - Prediger, Rui D S
AU  - Prediger RD
FAU - Passos, Giselle F
AU  - Passos GF
FAU - Calixto, Joao B
AU  - Calixto JB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100201
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Antibodies)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nitrobenzenes)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Sulfonamides)
RN  - 0 (Tnfrsf1a protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (amyloid beta-protein (1-40))
RN  - 123653-11-2 (N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - *Amyloid beta-Peptides
MH  - Analysis of Variance
MH  - Animals
MH  - Antibodies/pharmacology
MH  - CREB-Binding Protein/metabolism
MH  - Cognition Disorders/*chemically induced
MH  - Cyclooxygenase 2/*metabolism
MH  - Dinoprostone/metabolism
MH  - Disease Models, Animal
MH  - Electrophoretic Mobility Shift Assay/methods
MH  - Enzyme Inhibitors/pharmacology
MH  - Hippocampus/drug effects/metabolism
MH  - Maze Learning/drug effects/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nitrobenzenes/pharmacology
MH  - *Peptide Fragments
MH  - Protein Kinase C/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I/deficiency
MH  - Recognition, Psychology/drug effects/physiology
MH  - Signal Transduction/drug effects/genetics/*physiology
MH  - Sulfonamides/pharmacology
MH  - Tumor Necrosis Factor-alpha/immunology/*metabolism
MH  - Up-Regulation/drug effects/*physiology
EDAT- 2010/02/04 06:00
MHDA- 2010/05/26 06:00
CRDT- 2010/02/04 06:00
PHST- 2009/12/02 00:00 [received]
PHST- 2010/01/19 00:00 [revised]
PHST- 2010/01/24 00:00 [accepted]
PHST- 2010/02/04 06:00 [entrez]
PHST- 2010/02/04 06:00 [pubmed]
PHST- 2010/05/26 06:00 [medline]
AID - S0166-4328(10)00073-2 [pii]
AID - 10.1016/j.bbr.2010.01.040 [doi]
PST - ppublish
SO  - Behav Brain Res. 2010 May 1;209(1):165-73. doi: 10.1016/j.bbr.2010.01.040. Epub 
      2010 Feb 1.