PMID- 12814375
OWN - NLM
STAT- MEDLINE
DCOM- 20030904
LR  - 20190815
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 17
IP  - 11
DP  - 2003 Jun
TI  - Deficits in spatial learning and synaptic plasticity induced by the rapid and 
      competitive broad-spectrum cyclooxygenase inhibitor ibuprofen are reversed by 
      increasing endogenous brain-derived neurotrophic factor.
PG  - 2438-46
AB  - Cyclooxygenase (COX), which is present in two isoforms (COX1 and 2), synthesizes 
      prostaglandins from arachidonic acid; it plays a crucial role in inflammation in 
      both central and peripheral tissues. Here, we describe its role in synaptic 
      plasticity and spatial learning in vivo via an effect on brain-derived 
      neurotrophic factor (BDNF) and prostaglandin E2 (PGE2; both measured by Elisa). 
      We found that broad-spectrum COX inhibition (BSCI) inhibits the induction of 
      long-term potentiation (LTP; the major contemporary model of synaptic 
      plasticity), and causes substantial and sustained deficits in spatial learning in 
      the watermaze. Increases in BDNF and PGE2 following spatial learning and LTP were 
      also blocked. Importantly, 4 days of prior exercise in a running wheel increased 
      endogenous BDNF levels sufficiently to reverse the BSCI of LTP and spatial 
      learning, and restored a parallel increase in LTP and learning-related BDNF and 
      PGE2. In control experiments, we found that BSCI had no effect on baseline 
      synaptic transmission or on the nonhippocampal visible-platform task; there was 
      no evidence of gastric ulceration from BSCI. COX2 is inhibited by glucorticoids; 
      there was no difference in blood corticosterone levels as measured by 
      radioimmunoassay in any condition. Thus, COX plays a previously undescribed, 
      permissive role in synaptic plasticity and spatial learning via a BDNF-associated 
      mechanism.
FAU - Shaw, Kendra N
AU  - Shaw KN
AD  - Department of Psychology and Trinity College Institute of Neuroscience, Trinity 
      College, Dublin 2, Ireland.
FAU - Commins, Sean
AU  - Commins S
FAU - O'Mara, Shane M
AU  - O'Mara SM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - W980KJ009P (Corticosterone)
RN  - WK2XYI10QM (Ibuprofen)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Corticosterone/blood
MH  - Cyclooxygenase Inhibitors/*pharmacology
MH  - Dinoprostone/analysis
MH  - Discrimination Learning/*drug effects/physiology
MH  - Ibuprofen/*pharmacology
MH  - Immunoenzyme Techniques/methods
MH  - Long-Term Potentiation/drug effects
MH  - Male
MH  - Neuronal Plasticity/*drug effects/physiology
MH  - Physical Conditioning, Animal/methods
MH  - Rats
MH  - Rats, Wistar
MH  - Spatial Behavior/drug effects
MH  - Synaptic Transmission/drug effects
MH  - Time Factors
EDAT- 2003/06/20 05:00
MHDA- 2003/09/05 05:00
CRDT- 2003/06/20 05:00
PHST- 2003/06/20 05:00 [pubmed]
PHST- 2003/09/05 05:00 [medline]
PHST- 2003/06/20 05:00 [entrez]
AID - 2643 [pii]
AID - 10.1046/j.1460-9568.2003.02643.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2003 Jun;17(11):2438-46. doi: 10.1046/j.1460-9568.2003.02643.x.