Evidence map›Paper›PMID 34984634›Full record

ArticleGeroScience2022

Pharmacologic treatment with OKN-007 reduces alpha-motor neuron loss in spinal cord of aging mice.

Katarzyna M Piekarz, Constantin Georgescu, Jonathan D Wren, Rheal A Towner, Holly Van Remmen

Open access · greenAbstract read
In one paragraph

Article in GeroScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 41% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Katarzyna M PiekarzOU Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA.
Constantin GeorgescuGenes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
Jonathan D WrenOU Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA.
Rheal A TownerOU Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA.
Holly Van RemmenOU Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA. Holly-VanRemmen@omrf.org.
Oklahoma Medical Research Foundation · USUniversity of Oklahoma Health Sciences Center · US

Funding

Targeted DNA Methylation and Mitochondrial Heteroplasmy CoreP30AG050911 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI William Edmund Sonntag · 2015 to 2026
$13.9M
TRANSGENIC ANIMAL CORE SUBCONTRACT WITH UTHSC AT SAN ANTONIOP01AG020591 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI BROOKS, SUSAN V · 2002 to 2014
$10.7M
PROJECT 3: Neuromuscular redox homeostasis in mice lacking SOD1 and aging wild type mice subcontract at University of LiverpoolP01AG051442 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BROOKS, SUSAN V · 2016 to 2020
$8.9M
Defining the relative roles of pre- and post-synaptic events in the initiation and progression of sarcopeniaR01AG050676 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BROOKS, SUSAN V, VAN REMMEN, HOLLY · 2016 to 2020
$3.3M
BLR&D Research Career Scientist Award ApplicationIK6BX005234 · VA · OKLAHOMA CITY VA MEDICAL CENTER · PI VAN REMMEN, HOLLY · 2020 to 2024
–
BLRD VA IK6 BX005234NIA NIH HHS P01 AG020591NIA NIH HHS P01 AG051442NIA NIH HHS P30 AG050911NIA NIH HHS R01 AG050676
6 · The paper itself

Abstract

Aging is associated with molecular and functional declines in multiple physiologic systems. We have previously reported age-related changes in spinal cord that included a decline in α-motor neuron numbers, axonal loss, and demyelination associated with increased inflammation and blood-spinal cord barrier (BSCB) permeability. These changes may influence other pathologies associated with aging, in particular loss of muscle mass and function (sarcopenia), which we and others have shown is accompanied by neuromuscular junction disruption and loss of innervation. Interventions to protect and maintain motor neuron viability and function in aging are currently lacking and could have a significant impact on improving healthspan. Here we tested a promising compound, OKN-007, that has known antioxidant, anti-inflammatory and neuroprotective properties, as a potential intervention in age-related changes in the spinal cord. OKN-007 is a low molecular weight disulfonyl derivative of (N-tert Butyl-α-phenylnitrone) (PBN) that can easily cross the blood-brain barrier. We treated middle age (16 month) wild-type male mice with OKN-007 in drinking water at a dose of 150 mg/kg/day until 25 months of age. OKN-007 treatment exerted a number of beneficial effects in the aging spinal cord, including a 35% increase in the number of lumbar α-motor neurons in OKN-treated old mice compared to age-matched controls. Brain spinal cord barrier permeability, which is increased in aging spinal cord, was also blunted by OKN-007 treatment. Age-related changes in microglia proliferation and activation are blunted by OKN-007, while we found no effect on astrocyte proliferation. Transcriptome analysis identified expression changes in a number of genes that are involved in neuronal structure and function and revealed a subset of genes whose changes in response to aging are reversed by OKN-007 treatment. Overall, our findings suggest that OKN-007 exerts neuroprotective and anti-inflammatory effects on the aging spinal cord and support OKN-007 as a potential therapeutic to improve α-motor neuron health.

Indexed as

Motor NeuronsSpinal CordAgingAnimalsBenzenesulfonatesIminesMaleMiceNeuromuscular JunctionBenzenesulfonatesIminesOKN 007AgingBlood spinal cord permeabilityMicrogliaMotor neuronsOKN-007

Identifiers

PMID34984634
PMCPMC8811061
OpenAlexW4206126651

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.