Evidence map›Paper›PMID 24440642›Full record

ArticleExperimental neurology2014

Astroglial heme oxygenase-1 and the origin of corpora amylacea in aging and degenerating neural tissues.

Wei Song, Hillel Zukor, Adrienne Liberman, Sagi Kaduri, Zoe Arvanitakis, David A Bennett, Hyman M Schipper

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
1.3field-weighted citation impact, top 21% 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

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.

  1. Guideline
  2. Guideline
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Religious Orders Study and Rush Memory and Aging Project.Journal of Alzheimer's disease : JAD · 2018
    Review
  17. Review
  18. Article
  19. Article
  20. Review
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 3 institutions in 2 countries.

Wei SongLady Davis Institute, Jewish General Hospital, 3755 Cote Ste. Catherine Road, Montreal, Quebec H3T 1E2, Canada.
Hillel ZukorLady Davis Institute, Jewish General Hospital, 3755 Cote Ste. Catherine Road, Montreal, Quebec H3T 1E2, Canada; Dept. of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 2B4, Canada.
Adrienne LibermanLady Davis Institute, Jewish General Hospital, 3755 Cote Ste. Catherine Road, Montreal, Quebec H3T 1E2, Canada.
Sagi KaduriLady Davis Institute, Jewish General Hospital, 3755 Cote Ste. Catherine Road, Montreal, Quebec H3T 1E2, Canada.
Zoe ArvanitakisRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA.
Hyman M SchipperLady Davis Institute, Jewish General Hospital, 3755 Cote Ste. Catherine Road, Montreal, Quebec H3T 1E2, Canada; Dept. of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 2B4, Canada. Electronic address: hyman.schipper@mcgill.ca.
Jewish General Hospital · CARush University Medical Center · USMcGill University · CA

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Vascular Cognitive and Motor Decline: Impact of aPLR01AG040039 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI ARVANITAKIS, ZOE · 2011 to 2015
$2.9M
CIHRNIA NIH HHS P30 AG010161NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG040039
6 · The paper itself

Abstract

backgroundCorpora amylacea (CA) are glycoproteinaceous (predominantly glial and extracellular) inclusions that accumulate in normal aging brain and, to a greater extent, in Alzheimer disease (AD). Previous pharmacological evidence suggested that up-regulation of endogenous heme oxygenase-1 (HO-1) in astrocytes promotes transformation of normal mitochondria to CA-like inclusions. Here, we determined whether 1) HMOX1 transfection fosters the accumulation of CA-like inclusions in cultured rat astroglia; 2) the HMOX1 transgene promotes CA formation in the brains of aging GFAP.HMOX1 mice; and 3) brain mitochondrial damage and CA biogenesis are augmented in persons with mild cognitive impairment (MCI), a harbinger of AD.

methodsCA were ascertained in (i) neonatal rat astroglia transfected with flag-tagged human HO-1 cDNA, (ii) brain sections derived from 19month-old GFAP.HMOX1 and wild-type (WT) mice, and (iii) post-mortem hippocampal sections from individuals with mild (MCI) and no cognitive impairment (NCI) after staining with PAS or antisera against HO-1, ubiquitin (Ub), manganese superoxide dismutase (MnSOD), and α-synuclein or tyrosine hydroxylase (TH).

resultsHMOX1 transfection induced cytoplasmic vacuolation and the accumulation of PAS+ inclusions in cultured astroglia. Numerous CA-like inclusions stained with PAS and immunoreactive for HO-1, Ub and MnSOD were observed in the brains of GFAP.HMOX1 mice, but were rarely encountered in age-matched, WT controls. Numbers of HO-1-positive CA were significantly increased in certain hippocampal strata of MCI subjects relative to NCI preparations. MnSOD and Ub proteins co-localized to CA in both the control and MCI specimens.

conclusionsHO-1 promotes mitochondrial damage and CA biogenesis in astrocyte cultures and in the intact aging brain. CA formation is enhanced in the MCI hippocampus and thus occurs relatively early in the pathogenesis of AD. Glial HO-1 suppression may attenuate bioenergetic failure and slow disease progression in AD and other neurodegenerative conditions featuring accelerated accumulation of CA.

Indexed as

AgedAged, 80 and overAgingAnimalsAnimals, NewbornAstrocytesCognitive DysfunctionFemaleGlycoproteinsGreen Fluorescent ProteinsHeme Oxygenase-1HippocampusHumansInclusion BodiesMaleMembrane ProteinsGlycoproteinsGreen Fluorescent ProteinsHeme Oxygenase-1HMOX1 protein, humanHmox1 protein, mouseMembrane ProteinsAlzheimer diseaseAstrocyteCorpora amylaceaHeme oxygenase-1Mild cognitive impairmentMitochondriaTransgenic mice

Identifiers

PMID24440642
PMCPMC4020524
OpenAlexW2004756981

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.