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Pharmacological inhibition of FAAH modulates TLR-induced neuroinflammation, but not sickness behaviour: An effect partially mediated by central TRPV1

Overview of attention for article published in Brain, Behavior & Immunity, May 2017
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Title
Pharmacological inhibition of FAAH modulates TLR-induced neuroinflammation, but not sickness behaviour: An effect partially mediated by central TRPV1
Published in
Brain, Behavior & Immunity, May 2017
DOI 10.1016/j.bbi.2017.02.016
Pubmed ID
Authors

Rebecca J. Henry, Daniel M. Kerr, Lisa E. Flannery, Marykate Killilea, Edel M. Hughes, Louise Corcoran, David P. Finn, Michelle Roche

Abstract

Aberrant activation of toll-like receptors (TLRs), key components of the innate immune system, has been proposed to underlie and exacerbate a range of central nervous system disorders. Increasing evidence supports a role for the endocannabinoid system in modulating inflammatory responses including those mediated by TLRs, and thus this system may provide an important treatment target for neuroinflammatory disorders. However, the effect of modulating endocannabinoid tone on TLR-induced neuroinflammation in vivo and associated behavioural changes is largely unknown. The present study examined the effect of inhibiting fatty acid amide hydrolyase (FAAH), the primary enzyme responsible for the metabolism of anandamide (AEA), in vivo on TLR4-induced neuroimmune and behavioural responses, and evaluated sites and mechanisms of action. Systemic administration of the FAAH inhibitor PF3845 increased levels of AEA, and related FAAH substrates N-oleoylethanolamide (OEA) and N-palmitoylethanolamide (PEA), in the frontal cortex and hippocampus of rats, an effect associated with an attenuation in the expression of pro- and anti-inflammatory cytokines and mediators measured 2hrs following systemic administration of the TLR4 agonist, lipopolysaccaharide (LPS). These effects were mimicked by central i.c.v. administration of PF3845, but not systemic administration of the peripherally-restricted FAAH inhibitor URB937. Central antagonism of TRPV1 significantly attenuated the PF3845-induced decrease in IL-6 expression, effects not observed following antagonism of CB1, CB2, PPARα, PPARγ or GPR55. LPS-induced a robust sickness-like behavioural response and increased the expression of markers of glial activity and pro-inflammatory cytokines over 24hrs. Systemic administration of PF3845 modulated the TLR4-induced expression of neuroimmune mediators and anhedonia without altering acute sickness behaviour. Overall, these findings support an important role for FAAH substrates directly within the brain in the regulation of TLR4-associated neuroinflammation and highlight a role for TRPV1 in partially mediating these effects.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 19%
Student > Bachelor 6 19%
Researcher 4 13%
Student > Doctoral Student 3 10%
Student > Master 3 10%
Other 5 16%
Unknown 4 13%
Readers by discipline Count As %
Neuroscience 8 26%
Pharmacology, Toxicology and Pharmaceutical Science 5 16%
Biochemistry, Genetics and Molecular Biology 3 10%
Medicine and Dentistry 3 10%
Immunology and Microbiology 3 10%
Other 4 13%
Unknown 5 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 February 2017.
All research outputs
#7,632,429
of 12,211,903 outputs
Outputs from Brain, Behavior & Immunity
#1,142
of 1,779 outputs
Outputs of similar age
#150,904
of 259,295 outputs
Outputs of similar age from Brain, Behavior & Immunity
#49
of 78 outputs
Altmetric has tracked 12,211,903 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,779 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.5. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 259,295 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 78 others from the same source and published within six weeks on either side of this one. This one is in the 29th percentile – i.e., 29% of its contemporaries scored the same or lower than it.