Evidence map›Paper›PMID 38600510›Full record

ArticleJournal of neuroinflammation2024

Constitutive knockout of interleukin-6 ameliorates memory deficits and entorhinal astrocytosis in the MRL/lpr mouse model of neuropsychiatric lupus.

Joshua Reynolds, Michelle Huang, Yaxi Li, Myriam Meineck, Tamara Moeckel, Julia Weinmann-Menke, Chandra Mohan, Andreas Schwarting, Chaim Putterman

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

Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
8.5field-weighted citation impact, top 2% 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

15 citing papers in PubMed, 18 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

9 authors at 4 institutions in 3 countries.

Joshua ReynoldsAlbert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, NY, USA.
Michelle HuangAlbert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, NY, USA.
Yaxi LiUniversity of Houston, Houston, TX, USA.
Myriam MeineckUniversity Medical Center of the Johannes Gutenberg University, University of Mainz, Mainz, Germany.
Tamara MoeckelUniversity Medical Center of the Johannes Gutenberg University, University of Mainz, Mainz, Germany.
Julia Weinmann-MenkeUniversity Medical Center of the Johannes Gutenberg University, University of Mainz, Mainz, Germany.
Chandra MohanUniversity of Houston, Houston, TX, USA.
Andreas SchwartingUniversity Medical Center of the Johannes Gutenberg University, University of Mainz, Mainz, Germany.
Chaim PuttermanAlbert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, NY, USA. chaim.putterman@biu.ac.il.
Albert Einstein College of Medicine · USUniversity Medical Center of the Johannes Gutenberg University Mainz · DEUniversity of Houston · USJohannes Gutenberg University Mainz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeuropsychiatric lupus (NPSLE) describes the cognitive, memory, and affective emotional burdens faced by many lupus patients. While NPSLE's pathogenesis has not been fully elucidated, clinical imaging studies and cerebrospinal fluid (CSF) findings, namely elevated interleukin-6 (IL-6) levels, point to ongoing neuroinflammation in affected patients. Not only linked to systemic autoimmunity, IL-6 can also activate neurotoxic glial cells the brain. A prior pre-clinical study demonstrated that IL-6 can acutely induce a loss of sucrose preference; the present study sought to assess the necessity of chronic IL-6 exposure in the NPSLE-like disease of MRL/lpr lupus mice.

methodsWe quantified 1308 proteins in individual serum or pooled CSF samples from MRL/lpr and control MRL/mpj mice using protein microarrays. Serum IL-6 levels were plotted against characteristic NPSLE neurobehavioral deficits. Next, IL-6 knockout MRL/lpr (IL-6 KO; n = 15) and IL-6 wildtype MRL/lpr mice (IL-6 WT; n = 15) underwent behavioral testing, focusing on murine correlates of learning and memory deficits, depression, and anxiety. Using qPCR, we quantified the expression of inflammatory genes in the cortex and hippocampus of MRL/lpr IL-6 KO and WT mice. Immunofluorescent staining was performed to quantify numbers of microglia (Iba1 +) and astrocytes (GFAP +) in multiple cortical regions, the hippocampus, and the amygdala.

resultsMRL/lpr CSF analyses revealed increases in IL-17, MCP-1, TNF-α, and IL-6 (a priori p-value < 0.1). Serum levels of IL-6 correlated with learning and memory performance (R

conclusionsThe inflammatory composition of MRL/lpr CSF resembles that of human NPSLE patients. Increased in the CNS, IL-6 is necessary to the development of learning and memory deficits in the MRL/lpr model of NPSLE. Furthermore, the stimulation of entorhinal astrocytosis appears to be a key mechanism by which IL-6 promotes these behavioral deficits.

Indexed as

Interleukin-6Lupus Erythematosus, SystemicLupus Vasculitis, Central Nervous SystemAnimalsDepressionGliosisMemory DisordersMiceMice, Inbred MRL lprInterleukin-6AstrocytosisEntorhinal cortexInterleukin-6Memory deficitsNPSLE

Identifiers

PMID38600510
PMCPMC11007930
OpenAlexW4394683158

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.