Evidence map›Paper›PMID 32703230›Full record

ArticleJournal of neuroinflammation2020

Three-dimensional morphometric analysis reveals time-dependent structural changes in microglia and astrocytes in the central amygdala and hypothalamic paraventricular nucleus of heart failure rats.

Ferdinand Althammer, Hildebrando Candido Ferreira-Neto, Myurajan Rubaharan, Ranjan K Roy, Atit A Patel, Anne Murphy, Daniel N Cox, Javier E Stern

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Ferdinand AlthammerCenter for Neuroinflammation and Cardiometabolic Diseases, Georgia State University, Atlanta, USA.
Hildebrando Candido Ferreira-NetoCenter for Neuroinflammation and Cardiometabolic Diseases, Georgia State University, Atlanta, USA.
Myurajan RubaharanNeuroscience Institute, Georgia State University, Atlanta, USA.
Ranjan K RoyCenter for Neuroinflammation and Cardiometabolic Diseases, Georgia State University, Atlanta, USA.
Atit A PatelNeuroscience Institute, Georgia State University, Atlanta, USA.
Anne MurphyNeuroscience Institute, Georgia State University, Atlanta, USA.
Daniel N CoxNeuroscience Institute, Georgia State University, Atlanta, USA.
Javier E SternCenter for Neuroinflammation and Cardiometabolic Diseases, Georgia State University, Atlanta, USA. jstern@gsu.edu.
Georgia State University · US

Funding

Anatomical characterization of neuronal cell types of the mouse brainU01MH114829 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ASCOLI, GIORGIO A, DONG, HONG-WEI · 2017 to 2021
$13.9M
Molecular and Computational Dissection of Cold NociceptionR01NS115209 · NINDS · GEORGIA STATE UNIVERSITY · PI GENNADY S CYMBALYUK, Daniel N Cox · 2019 to 2026
$3.5M
Cytoskeletal mechanisms of dendrite arbor shape developmentR01NS086082 · NINDS · GEORGIA STATE UNIVERSITY · PI ASCOLI, GIORGIO A, COX, DANIEL N · 2013 to 2023
$3.1M
Altered CNS Intercellular Signaling Mechanisms in Cardiovascular DiseaseR01HL090948 · NHLBI · UNIVERSITY OF CINCINNATI · PI STERN, JAVIER E · 2008 to 2017
$3.0M
Deutsche Forschungsgemeinschaft AL 2466/1-1NHLBI NIH HHS HL090948NHLBI NIH HHS R01 HL090948NIH HHS NIH NS086082 and NIH NS115209NIMH NIH HHS U01 MH114829NINDS NIH HHS R01 NS086082NINDS NIH HHS R01 NS115209
6 · The paper itself

Abstract

backgroundCardiovascular diseases, including heart failure, are the most common cause of death globally. Recent studies support a high degree of comorbidity between heart failure and cognitive and mood disorders resulting in memory loss, depression, and anxiety. While neuroinflammation in the hypothalamic paraventricular nucleus contributes to autonomic and cardiovascular dysregulation in heart failure, mechanisms underlying cognitive and mood disorders in this disease remain elusive. The goal of this study was to quantitatively assess markers of neuroinflammation (glial morphology, cytokines, and A1 astrocyte markers) in the central amygdala, a critical forebrain region involved in emotion and cognition, and to determine its time course and correlation to disease severity during the progression of heart failure.

methodsWe developed and implemented a comprehensive microglial/astrocyte profiler for precise three-dimensional morphometric analysis of individual microglia and astrocytes in specific brain nuclei at different time points during the progression of heart failure. To this end, we used a well-established ischemic heart failure rat model. Morphometric studies were complemented with quantification of various pro-inflammatory cytokines and A1/A2 astrocyte markers via qPCR.

resultsWe report structural remodeling of central amygdala microglia and astrocytes during heart failure that affected cell volume, surface area, filament length, and glial branches, resulting overall in somatic swelling and deramification, indicative of a change in glial state. These changes occurred in a time-dependent manner, correlated with the severity of heart failure, and were delayed compared to changes in the hypothalamic paraventricular nucleus. Morphometric changes correlated with elevated mRNA levels of pro-inflammatory cytokines and markers of reactive A1-type astrocytes in the paraventricular nucleus and central amygdala during heart failure.

conclusionWe provide evidence that in addition to the previously described hypothalamic neuroinflammation implicated in sympathohumoral activation during heart failure, microglia, and astrocytes within the central amygdala also undergo structural remodeling indicative of glial shifts towards pro-inflammatory phenotypes. Thus, our studies suggest that neuroinflammation in the amygdala stands as a novel pathophysiological mechanism and potential therapeutic target that could be associated with emotional and cognitive deficits commonly observed at later stages during the course of heart failure.

Indexed as

AnimalsAstrocytesCentral Amygdaloid NucleusHeart FailureImage Processing, Computer-AssistedImaging, Three-DimensionalMaleMicrogliaMicroscopy, ConfocalParaventricular Hypothalamic NucleusRatsRats, WistarA1AmygdalaAstrocytesAutonomicBehaviorCytokinesHeart failureHypothalamusMicrogliaNeuroinflammation

Identifiers

PMID32703230
PMCPMC7379770
OpenAlexW3044664147

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.