Evidence map›Paper›PMID 23399551›Full record

ArticleMolecular & cellular proteomics : MCP2013

Spatio-temporal analysis of molecular determinants of neuronal degeneration in the aging mouse cerebellum.

Erik L de Graaf, Wilbert P Vermeij, Monique C de Waard, Yvonne Rijksen, Ingrid van der Pluijm, Casper C Hoogenraad, Jan H J Hoeijmakers, A F Maarten Altelaar, Albert J R Heck

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

18 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Aging, Neurodegenerative Disorders, and Cerebellum.International journal of molecular sciences · 2024
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
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 2 countries.

Erik L de GraafBiomolecular Mass Spectrometry and Proteomics Group, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Wilbert P Vermeij
Monique C de Waard
Yvonne Rijksen
Ingrid van der Pluijm
Casper C Hoogenraad
Jan H J Hoeijmakers
A F Maarten Altelaar
Albert J R Heck
Center for Human Genetics · USUtrecht University · NLCancer Genomics Centre · NLErasmus University Rotterdam · NL

Funding

THE IMPACT OF CELLULAR DEFENSE ON THE ROLE OF Ku80 IN GENOME MAINTENANCE AND LONGP01AG017242 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI VIJG, JAN · 1999 to 2023
$46.1M
Models for DNA repair and cell cycle control variantsU01ES011044 · NIEHS · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI VIJG, JAN · 2001 to 2006
$5.1M
NIA NIH HHS 1P01 AG-17242-02NIA NIH HHS P01 AG017242NIEHS NIH HHS 1UO1 ES011044NIEHS NIH HHS U01 ES011044
6 · The paper itself

Abstract

The accumulation of cellular damage, including DNA damage, is hypothesized to contribute to aging-related neurodegenerative changes. DNA excision repair cross-complementing group 1 (Ercc1) knock-out mice represent an accepted model of neuronal aging, showing gradual neurodegenerative changes, including loss of synaptic contacts and cell body shrinkage. Here, we used the Purkinje cell-specific Ercc1 DNA-repair knock-out mouse model to study aging in the mouse cerebellum. We performed an in-depth quantitative proteomics analysis, using stable isotope dimethyl labeling, to decipher changes in protein expression between the early (8 weeks), intermediate (16 weeks), and late (26 weeks) stages of the phenotypically aging Ercc1 knock-out and healthy littermate control mice. The expression of over 5,200 proteins from the cerebellum was compared quantitatively, whereby 79 proteins (i.e. 1.5%) were found to be substantially regulated during aging. Nearly all of these molecular markers of the early aging onset belonged to a strongly interconnected network involved in excitatory synaptic signaling. Using immunohistological staining, we obtained temporal and spatial profiles of these markers confirming not only the proteomics data but in addition revealed how the change in protein expression correlates to synaptic changes in the cerebellum. In summary, this study provides a highly comprehensive spatial and temporal view of the dynamic changes in the cerebellum and Purkinje cell signaling in particular, indicating that synapse signaling is one of the first processes to be affected in this premature aging model, leading to neuron morphological changes, neuron degeneration, inflammation, and ultimately behavior disorders.

Indexed as

AgingAnimalsCell ShapeCerebellumDNA-Binding ProteinsDNA RepairEndonucleasesFemaleMaleMiceMice, Inbred C57BLMice, KnockoutNerve DegenerationNerve Tissue ProteinsProteomePurkinje CellsDNA-Binding ProteinsEndonucleasesErcc1 protein, mouseNerve Tissue ProteinsProteome

Identifiers

PMID23399551
PMCPMC3650344
OpenAlexW2133325335

What OpenQuestion holds

Textmetadata
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.