Evidence map›Paper›PMID 27190010›Full record

ArticleBrain : a journal of neurology2016

Cyclooxygenase inhibition targets neurons to prevent early behavioural decline in Alzheimer's disease model mice.

Nathaniel S Woodling, Damien Colas, Qian Wang, Paras Minhas, Maharshi Panchal, Xibin Liang, Siddhita D Mhatre, Holden Brown, Novie Ko, Irene Zagol-Ikapitte and 10 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 106 citations in OpenAlex.

  1. No apparent effect of naproxen on CSF markers of innate immune activation.Annals of clinical and translational neurology · 2019
    Trial
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Effects ofJournal of microbiology and biotechnology · 2025
    Article
  10. Effects of Long-Term Carprofen and Omeprazole Administration in C57BL/6J Mice.Journal of the American Association for Laboratory Animal Science : JAALAS · 2025
    Article
  11. Article
  12. Review
  13. Efficacy and Mechanism ofNutrients · 2024
    Article
  14. Review
  15. Review
  16. Review
  17. RSC advances · 2023
    Article
  18. Article
  19. Exploring the role of COX-2 in Alzheimer's disease: Potential therapeutic implications of COX-2 inhibitors.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023
    Review
  20. Article

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 1 institution in 1 country.

Nathaniel S Woodling1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA 2 Neurosciences Graduate Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
Damien Colas1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Qian Wang1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Paras Minhas1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA 1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Maharshi Panchal1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Xibin Liang1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Siddhita D Mhatre1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Holden Brown1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA 4 Brains On-line LLC, South San Francisco, CA, USA.
Novie Ko1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Irene Zagol-Ikapitte1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Marieke van der Hart1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Taline V Khroyan1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Bayarsaikhan Chuluun1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Prachi G Priyam1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ginger L Milne1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Arash Rassoulpour1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Olivier Boutaud1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Amy B Manning-Boğ1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
H Craig Heller1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Katrin I Andreasson1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA kandreas@stanford.edu.
Stanford University · US

Funding

Working Memory in Parkinson Disease: A Cognitive & Systems Neuroscience ApproachP50AG047366 · NIA · STANFORD UNIVERSITY · PI HENDERSON, VICTOR · 2015 to 2019
$7.9M
VECTOR COREP30NS069375 · NINDS · STANFORD UNIVERSITY · PI STEINBERG, GARY K · 2011 to 2019
$6.3M
Targeting the kynurenine pathway in Alzheimer's diseaseR01AG048232 · NIA · STANFORD UNIVERSITY · PI ANDREASSON, KATRIN I. · 2014 to 2018
$2.4M
Prostanoid signaling and inflammation in aging and Alzheimer's diseaseR01AG030209 · NIA · STANFORD UNIVERSITY · PI ANDREASSON, KATRIN I. · 2009 to 2013
$1.6M
Validation of the PGE2 EP4 receptor as a therapeutic target in ADR21AG033914 · NIA · STANFORD UNIVERSITY · PI ANDREASSON, KATRIN I. · 2009 to 2010
$892k
Targeting protein adduction by reactive aldehydes in Alzheimer's diseaseR21AG042194 · NIA · STANFORD UNIVERSITY · PI ANDREASSON, KATRIN I., BOUTAUD, OLIVIER · 2012 to 2013
$441k
Cellular and Molecular Mechanisms of Inflammation in Alzheimer's DiseaseF31AG039195 · NIA · STANFORD UNIVERSITY · PI WOODLING, NATHANIEL S · 2011 to 2012
$55k
NIA NIH HHS F31 AG039195NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG030209NIA NIH HHS R01 AG048232NIA NIH HHS R21 AG033914NIA NIH HHS R21 AG042194NINDS NIH HHS N01 NS002331NINDS NIH HHS P30 NS069375
6 · The paper itself

Abstract

Identifying preventive targets for Alzheimer's disease is a central challenge of modern medicine. Non-steroidal anti-inflammatory drugs, which inhibit the cyclooxygenase enzymes COX-1 and COX-2, reduce the risk of developing Alzheimer's disease in normal ageing populations. This preventive effect coincides with an extended preclinical phase that spans years to decades before onset of cognitive decline. In the brain, COX-2 is induced in neurons in response to excitatory synaptic activity and in glial cells in response to inflammation. To identify mechanisms underlying prevention of cognitive decline by anti-inflammatory drugs, we first identified an early object memory deficit in APPSwe-PS1ΔE9 mice that preceded previously identified spatial memory deficits in this model. We modelled prevention of this memory deficit with ibuprofen, and found that ibuprofen prevented memory impairment without producing any measurable changes in amyloid-β accumulation or glial inflammation. Instead, ibuprofen modulated hippocampal gene expression in pathways involved in neuronal plasticity and increased levels of norepinephrine and dopamine. The gene most highly downregulated by ibuprofen was neuronal tryptophan 2,3-dioxygenase (Tdo2), which encodes an enzyme that metabolizes tryptophan to kynurenine. TDO2 expression was increased by neuronal COX-2 activity, and overexpression of hippocampal TDO2 produced behavioural deficits. Moreover, pharmacological TDO2 inhibition prevented behavioural deficits in APPSwe-PS1ΔE9 mice. Taken together, these data demonstrate broad effects of cyclooxygenase inhibition on multiple neuronal pathways that counteract the neurotoxic effects of early accumulating amyloid-β oligomers.

Indexed as

Alzheimer DiseaseAnimalsBehavior, AnimalCyclooxygenase InhibitorsDisease Models, AnimalDown-RegulationElectroencephalographyGene ExpressionHippocampusIbuprofenMaleMemory DisordersMiceMice, Inbred C57BLNeuronal PlasticityNeuronsCyclooxygenase InhibitorsIbuprofenTryptophan OxygenaseAlzheimer’s diseasecyclooxgenaseshippocampusibuprofenkynurenine pathway

Identifiers

PMID27190010
PMCPMC4939702
OpenAlexW2363424999

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.