Evidence map›Paper›PMID 31238091›Full record

ArticleNeurobiology of disease2019

Mitochondrial biogenesis is altered in HIV+ brains exposed to ART: Implications for therapeutic targeting of astroglia.

Mary K Swinton, Aliyah Carson, Francesca Telese, Ana B Sanchez, Benchawanna Soontornniyomkij, Leila Rad, Isabella Batki, Brandi Quintanilla, Josué Pérez-Santiago, Cristian L Achim and 5 more

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

Article in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 2 pooled it
3.8field-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

35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.

  1. Pooled it
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  16. Observational
  17. Immune Cell Metabolic Fitness for Life.Antibodies (Basel, Switzerland) · 2022
    Review
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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

15 authors at 2 institutions in 2 countries.

Mary K SwintonDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Aliyah CarsonDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Francesca TeleseDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Ana B SanchezDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Benchawanna SoontornniyomkijDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Leila RadDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Isabella BatkiDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Brandi QuintanillaDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Josué Pérez-SantiagoComprehensive Cancer Center, University of Puerto Rico, San Juan, PR, USA.
Cristian L AchimDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA; Department of Pathology, University of California San Diego, La Jolla, CA, USA.
Scott LetendreDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA; Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Ronald J EllisDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA; Department of Neuroscience, University of California San Diego, La Jolla, CA, USA.
Igor GrantDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Anne N MurphyDepartment of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Jerel Adam FieldsDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA. Electronic address: jafields@ucsd.edu.
University of California San Diego · USUniversity of Puerto Rico System · PR

Funding

STRUCTURAL NEUROIMAGING COREP30MH062512 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jennifer E Iudicello · 2001 to 2026
$50.4M
Translational Methamphetamine AIDS Research Center (TMARC)P50DA026306 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GRANT, IGOR · 2009 to 2018
$33.9M
The Manhattan HIV Brain BankU24MH100931 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MORGELLO, SUSAN · 2013 to 2023
$14.0M
California NeuroAIDS Tissue NetworkU24MH100928 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ACHIM, CRISTIAN L, MOORE, DAVID J · 2013 to 2023
$13.9M
NATIONAL NEUROLOGICAL AIDS BANKU24MH100929 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SINGER, ELYSE J · 2013 to 2023
$12.5M
Texas NeuroAIDS Research CenterU24MH100930 · NIMH · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GELMAN, BENJAMIN B. · 2013 to 2023
$12.1M
NNTC Data Coordinating CenterU24MH100925 · NIMH · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI FOX, HOWARD S, SHERMAN, SETH · 2013 to 2022
$9.5M
Brain Amyloid and HAND in the cART eraR01MH105319 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ACHIM, CRISTIAN L · 2015 to 2019
$2.5M
Mitochondrial biogenesis dysfunction in the CNS of HIV-infected individuals on antiretroviral therapyK01MH115819 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIELDS, JEREL ADAM · 2018 to 2020
$480k
Development of Pirenzepine for HIV-SNR41NS105177 · NINDS · WINSANTOR, INC. · PI FIELDS, JEREL ADAM, MIZISIN, ANDREW · 2017 to 2017
$466k
NIDA NIH HHS P50 DA026306NIMHD NIH HHS L60 MD013161NIMH NIH HHS K01 MH115819NIMH NIH HHS P30 MH062512NIMH NIH HHS R01 MH105319NIMH NIH HHS U24 MH100925NIMH NIH HHS U24 MH100928NIMH NIH HHS U24 MH100929NIMH NIH HHS U24 MH100930NIMH NIH HHS U24 MH100931NINDS NIH HHS R41 NS105177
6 · The paper itself

Abstract

The neuropathogenesis of HIV associated neurocognitive disorders (HAND) involves disruption of mitochondrial homeostasis and increased neuroinflammation. However, it is unknown if alterations in mitochondrial biogenesis in the brain underlie the neuropathogenesis of HAND. In this study, neuropathological and molecular analyses of mitochondrial biogenesis and inflammatory pathways were performed in brain specimens from a well-characterized cohort of HIV+ cases that were on antiretroviral regimens. In vitro investigations using primary human astroglia and neurons were used to probe the underlying mechanisms of mitochondrial alterations. In frontal cortices from HAND brains compared to cognitive normal brains, total levels of transcription factors that regulate mitochondrial biogenesis, peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and transcription factor A, mitochondrial (TFAM) were decreased. Immunohistochemical analyses revealed that TFAM was decreased in neurons and increased in astroglia. These changes were accompanied by decreased total mitochondrial DNA per cell and increased levels of messenger RNA for the proinflammatory cytokine interleukin (IL)-1β. To determine how IL-1β affects astroglial bioenergetic processes and mitochondrial activity, human astroglial cultures were exposed to recombinant IL-1β. IL-1β induced mitochondrial activity within 30 min of treatment, altered mitochondrial related gene expression, altered mitochondrial morphology, enhanced adenoside triphosphate (ATP) utilization and increased the expression of inflammatory cytokines. WIN55,212-2 (WIN), an aminoalkylindole derivative and cannabinoid receptor agonist, blocked IL-1β-induced bioenergetic fluctuations and inflammatory gene expression in astroglia independent of cannabinoid receptor (CB)1 and peroxisome proliferator-activated receptor (PPAR) γ. A PPARα antagonist reversed the anti-inflammatory effects of WIN in human astroglia. These results show that mitochondrial biogenesis is differentially regulated in neurons and astroglia in HAND brains and that targeting astroglial bioenergetic processes may be a strategy to modulate neuroinflammation.

Indexed as

Organelle BiogenesisAnti-HIV AgentsAstrocytesBrainCells, CulturedDNA-Binding ProteinsHIV SeropositivityHumansInflammationInterleukin-1betaMitochondriaMitochondrial ProteinsNeuronsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaTranscription FactorsAnti-HIV AgentsDNA-Binding ProteinsInterleukin-1betaMitochondrial ProteinsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPPARGC1A protein, humanTFAM protein, humanTranscription Factors

Identifiers

PMID31238091
PMCPMC6714553
OpenAlexW2950043708

What OpenQuestion holds

Textmetadata
LicenceTDM
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.