Evidence map›Paper›PMID 25447942›Full record

ArticleExperimental neurology2015

An in vitro assay to study induction of the regenerative state in sensory neurons.

E Frey, V Valakh, S Karney-Grobe, Y Shi, J Milbrandt, A DiAntonio

Abstract read
In one paragraph

Article in Experimental neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

36 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  19. Experimental Model Systems for Understanding Human Axonal Injury Responses.International journal of molecular sciences · 2021
    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

6 authors.

E FreyDepartment of Developmental Biology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: erin.frey@wustl.edu.
V ValakhDepartment of Developmental Biology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: vvalakh@wustl.edu.
S Karney-GrobeDepartment of Developmental Biology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: karney-grobe@wustl.edu.
Y ShiDepartment of Developmental Biology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: popstone07@gmail.com.
J MilbrandtDepartment of Genetics, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: jmilbrandt@wustl.edu.
A DiAntonioDepartment of Developmental Biology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: diantonio@wustl.edu.

Funding

Quantitative Neuroscience: Tools for Bridging Levels of AnalysisT32NS007292 · NINDS · BRANDEIS UNIVERSITY · PI GINA G TURRIGIANO · 1986 to 2026
$12.7M
Regulation of axonal degeneration by the DLK kinaseR37NS065053 · NINDS · WASHINGTON UNIVERSITY · PI Aaron Diantonio · 2020 to 2026
$4.3M
REGULATION OF AXONAL DEGENERATION BY THE DLK KINASER01NS065053 · NINDS · WASHINGTON UNIVERSITY · PI DIANTONIO, AARON · 2010 to 2019
$3.3M
A HIGH-THROUGHPUT ASSAY FOR PRECONDITIONING FACTORS THAT PROMOTE AXONAL REGENERATR33NS087562 · NINDS · WASHINGTON UNIVERSITY · PI DIANTONIO, AARON, MILBRANDT, JEFFREY D · 2016 to 2017
$1.1M
A HIGH-THROUGHPUT ASSAY FOR PRECONDITIONING FACTORS THAT PROMOTE AXONAL REGENERATR21NS087562 · NINDS · WASHINGTON UNIVERSITY · PI DIANTONIO, AARON, MILBRANDT, JEFFREY D · 2014 to 2015
$418k
NINDS NIH HHS NIH NS065053NINDS NIH HHS NIH NS087562NINDS NIH HHS R01 NS065053NINDS NIH HHS R21 NS087562NINDS NIH HHS R33 NS087562NINDS NIH HHS R37 NS065053NINDS NIH HHS T32 NS007292
6 · The paper itself

Abstract

After injury, peripheral neurons activate a pro-regenerative program that facilitates axon regeneration. While many regeneration-associated genes have been identified, the mechanism by which injury activates this program is less well understood. Furthermore, identifying pharmacological methods to induce a pro-regenerative state could lead to novel treatments to repair the injured nervous system. Therefore, we have developed an in vitro assay to study induction of the pro-regenerative state following injury or pharmacological treatment. First, we took advantage of the observation that dissociating and culturing sensory neurons from dorsal root ganglia activates a pro-regenerative program. We show that cultured neurons activate transcription factors and upregulate regeneration-associated genes common to the pro-regenerative program within the first hours after dissection. In a paradigm similar to pre-conditioning, neurons injured by dissociation display enhanced neurite outgrowth when replated as early as 12h after being removed from the animal. Furthermore, stimulation of the pro-regenerative state improves growth on inhibitory substrates and requires DLK/JNK signaling, both hallmarks of the pro-regeneration response in vivo. Finally, we modified this assay in order to identify new methods to activate the pro-regenerative state in an effort to mimic the pre-conditioning effect. We report that after several days in culture, neurons down-regulate many molecular hallmarks of injury and no longer display enhanced neurite outgrowth after replating. Hence, these neurons are functionally naïve and are a useful tool for identifying methods to induce the pro-regenerative state. We show that both injury and pre-treatment with forskolin reactivate the pro-regenerative state in this paradigm. Hence, this assay is useful for identifying pharmacological agents that induce the pro-regenerative state in the absence of injury.

Indexed as

AnimalsCells, CulturedGanglia, SpinalImmunohistochemistryIn Vitro TechniquesMiceMice, Inbred C57BLNerve RegenerationReal-Time Polymerase Chain ReactionSensory Receptor CellsAxon regenerationcJun N-terminal kinase (JNK)Dorsal root ganglion (DRG)Dual leucine zipper kinase (DLK)Replating assaySuperior cervical ganglion 10 (SCG10)

Identifiers

PMID25447942
PMCPMC4266464

What OpenQuestion holds

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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.