Evidence map›Paper›PMID 32602164›Full record

ArticleNeurourology and urodynamics2020

A possible mechanism underlying mood disorders associated with LUTS: Chronic bladder outlet obstruction causes NLRP3-dependent inflammation in the hippocampus and depressive behavior in rats.

Francis M Hughes, Nathan A Hirshman, Hamza A Malick, Simon W White, Huixia Jin, Shelby N Harper, J Todd Purves

Open access · greenAbstract read
In one paragraph

Article in Neurourology and urodynamics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

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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

7 authors at 1 institution in 1 country.

Francis M HughesDivision of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina.ORCID 0000-0003-3776-3653
Nathan A HirshmanDivision of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina.ORCID 0000-0002-5762-1209
Hamza A MalickDivision of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina.ORCID 0000-0002-8778-0374
Simon W WhiteDivision of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Huixia JinDivision of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina.ORCID 0000-0003-4645-2478
Shelby N HarperDivision of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina.ORCID 0000-0002-7996-6101
J Todd PurvesDivision of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina.ORCID 0000-0001-9689-2047
Duke Medical Center · US

Funding

Inflammation and neuropathy drive sex-specific diabetic bladder dysfunction in Akita miceR01DK117890 · NIDDK · DUKE UNIVERSITY · PI J. Todd Purves · 2019 to 2026
$2.5M
Inflammasomes Mediate Inflammation in Bladder Outlet ObstructionR01DK103534 · NIDDK · DUKE UNIVERSITY · PI PURVES, J. TODD · 2015 to 2018
$1.6M
NIDDK NIH HHS R01 DK103534NIDDK NIH HHS R01 DK117890
6 · The paper itself

Abstract

aimsReports link urinary dysfunction and mood disorders, such as depression, but a causative mechanism has never been postulated. Contemporary discoveries demonstrate a local inflammatory response in peripheral organs can trigger inflammation in the brain, particularly the hippocampus, mediated through the NLRP3 inflammasome. Critically, central inflammation causes depressive behavior. Since bladder outlet obstruction (BOO) evokes a local inflammatory response in the bladder, we hypothesize it will induce NLRP3-dependent inflammation in the hippocampus and depressive behavior.

methodsThere were four groups of rats: control, sham, BOO, or BOO + glyburide (an NLRP3 inhibitor). BOO was created by urethral ligation over a 1 mm catheter. Sham was tied loosely. Glyburide was provided by slow-release pellet (subcutaneous 50 mg, 21 day, replaced as needed). Rats were analyzed 12 weeks post-op for: hippocampal inflammation, microglial density, neurogenesis, and depression symptoms (open field and sucrose preference).

resultsBOO elicited hippocampal inflammation, accompanied by an increase in activated microglia (22%) and a decrease in neurogenesis (35%), which was blocked by glyburide. In addition, BOO rats displayed anxiety (57% decrease in exploratory behavior in the open field assay) and anhedonia (21% decrease in sucrose preference), two symptoms of depression. Like inflammation, these symptoms were diminished by glyburide to levels not statistically significantly different from controls.

conclusionsBOO, a bladder-localized event, stimulates NLRP3-dependent inflammation in the rat hippocampus after 12 weeks and this inflammation causes depressive behavior. This is the first mechanistic explanation of the link between BOO and depression and provides evidence for a distinct bladder-brain axis.

Indexed as

AnimalsDepressionDisease Models, AnimalFemaleHippocampusInflammasomesInflammationLower Urinary Tract SymptomsMicrogliaNLR Family, Pyrin Domain-Containing 3 ProteinRatsRats, Sprague-DawleyUrinary Bladder Neck ObstructionInflammasomesNLR Family, Pyrin Domain-Containing 3 Proteininflammasomesinflammationmood disordersurinary bladder

Identifiers

PMID32602164
PMCPMC8793365
OpenAlexW3038475976

What OpenQuestion holds

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Registered trials

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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.