PMID- 17556794
OWN - NLM
STAT- MEDLINE
DCOM- 20080117
LR  - 20200106
IS  - 1734-1140 (Print)
IS  - 1734-1140 (Linking)
VI  - 59
IP  - 2
DP  - 2007 Mar-Apr
TI  - Inhibitor of cyclooxygenase-2 protects against amyloid beta peptide-evoked memory 
      impairment in mice.
PG  - 164-72
AB  - Alzheimer's disease (AD) results in an impairment of memory and behavior. It is 
      accepted that amyloid beta (A beta) peptides are responsible for the 
      etiopathology of AD, but the precise signaling pathways leading to the disease 
      have not been elucidated. In this study, we have investigated the role of 
      cyclooxygenase-2 (COX-2) in A beta(1-42)-evoked memory impairment in mice. 
      Moreover, the effect of systemic inflammation on A beta-dependent locomotor and 
      memory disturbances has been evaluated. Twelve-month-old C57Bl6 mice were 
      injected intracerebroventricularly (icv) with A beta(1-42) alone or 
      simultaneously with intraperitoneal (ip) administration of lipopolysaccharide 
      (LPS). Some mice also received COX-2 inhibitor, NS-398. Another group of mice was 
      pretreated with LPS at 4 and 7 months of age, and then injected with A beta(1-42) 
      at 12 months of age. All mice were subjected to behavioral tests one week after A 
      beta administration. COX-2 protein level was analyzed in the hippocampus using 
      immunochemical method. Our data demonstrated that A beta enhanced COX-2 protein 
      level and decreased the locomotion and exploration in mice. Systemic inflammation 
      elevated COX-2 immunoreactivity at an early stage after injection and intensified 
      behavioral disturbances. Moreover, the object recognition in A beta-treated mice 
      was significantly affected compared to control mice. The administration of LPS 
      simultaneously with A beta worsened recognition performance. A COX-2 inhibitor 
      protected mice against memory deficit and locomotor disturbances. In 
      LPS-pretreated animals, A beta induced locomotor disturbances, but had no effect 
      on memory and COX-2 level. Our results indicate that A beta evokes enhancement of 
      COX-2 protein level and memory deficit. Systemic inflammation modulates A beta 
      effect on the brain function. The COX-2 inhibitor protects the brain against A 
      beta-induced memory disturbances.
FAU - Cakala, Magdalena
AU  - Cakala M
AD  - Department of Cellular Signalling, Medical Research Centre, Polish Academy of 
      Sciences, Pawinskiego 5, PL 02-106 Warszawa, Poland. magcakala@cmdik.pan.pl
FAU - Malik, Anna R
AU  - Malik AR
FAU - Strosznajder, Joanna B
AU  - Strosznajder JB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Pharmacol Rep
JT  - Pharmacological reports : PR
JID - 101234999
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Alzheimer Disease/*drug therapy
MH  - Amyloid beta-Peptides/*toxicity
MH  - Animals
MH  - Cyclooxygenase 2/physiology
MH  - Cyclooxygenase 2 Inhibitors/*therapeutic use
MH  - Disease Models, Animal
MH  - Exploratory Behavior/drug effects
MH  - Lipopolysaccharides/toxicity
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Motor Activity/drug effects
MH  - Peptide Fragments/*toxicity
EDAT- 2007/06/09 09:00
MHDA- 2008/01/18 09:00
CRDT- 2007/06/09 09:00
PHST- 2006/12/12 00:00 [received]
PHST- 2007/04/20 00:00 [revised]
PHST- 2007/06/09 09:00 [pubmed]
PHST- 2008/01/18 09:00 [medline]
PHST- 2007/06/09 09:00 [entrez]
PST - ppublish
SO  - Pharmacol Rep. 2007 Mar-Apr;59(2):164-72.