Evidence map›Paper›PMID 36931113›Full record

ArticleNeurobiology of aging2023

Chronic BMAA exposure combined with TDP-43 mutation elicits motor neuron dysfunction phenotypes in mice.

F J Arnold, M Burns, Y Chiu, J Carvalho, A D Nguyen, P C Ralph, A R La Spada, C L Bennett

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

Article in Neurobiology of aging, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.7field-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

11 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Challenges of modelling TDP-43 pathology in mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2025
    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

8 authors at 2 institutions in 1 country.

F J ArnoldDepartment of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA, USA; Department of Neurology, Duke University School of Medicine, Durham, NC, USA.
M BurnsDepartment of Neurology, Duke University School of Medicine, Durham, NC, USA; Departments of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA.
Y ChiuMolecular Education, Technology and Research Innovation Center, North Carolina State University, Raleigh, NC, USA.
J CarvalhoDepartment of Neurology, Duke University School of Medicine, Durham, NC, USA.
A D NguyenDepartment of Neurology, Duke University School of Medicine, Durham, NC, USA.
P C RalphDepartment of Neurology, Duke University School of Medicine, Durham, NC, USA.
A R La SpadaDepartment of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA, USA; Department of Neurology, Duke University School of Medicine, Durham, NC, USA; Departments of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA; Department of Neurology, University of California, Irvine, Irvine, CA, USA; Department of Biological Chemistry, University of California, Irvine, Irvine, CA, USA; UCI Center for Neurotherapeutics, University of California, Irvine, Irvine, CA, USA. Electronic address: alaspada@uci.edu.
C L BennettDepartment of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA, USA; Department of Neurology, Duke University School of Medicine, Durham, NC, USA. Electronic address: craiglb@uci.edu.
Duke University · USNorth Carolina State University · US

Funding

La Spada Outstanding Investigator AwardR35NS122140 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI ALBERT R LA SPADA · 2021 to 2026
$7.2M
NINDS NIH HHS R35 NS122140
6 · The paper itself

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with an average age-of-onset of ∼60 years and is usually fatal within 2-5 years of diagnosis. Mouse models based upon single gene mutations do not recapitulate all ALS pathological features. Environmental insults may also contribute to ALS, and β-N-methylamino-L-alanine (BMAA) is an environmental toxin linked with an increased risk of developing ALS. BMAA, along with cycasin, are hypothesized to be the cause of the Guam-ALS epicenter of the 1950s. We developed a multihit model based on low expression of a dominant familial ALS TDP-43 mutation (Q331K) and chronic low-dose BMAA exposure. Our two-hit mouse model displayed a motor phenotype absent from either lesion alone. By LC/MS analysis, free BMAA was confirmed at trace levels in brain, and were as high as 405 ng/mL (free) and 208 ng/mL (protein-bound) in liver. Elevated BMAA levels in liver were associated with dysregulation of the unfolded protein response (UPR) pathway. Our data represent initial steps towards an ALS mouse model resulting from combined genetic and environmental insult.

Indexed as

Amino Acids, DiaminoAmyotrophic Lateral SclerosisNeurodegenerative DiseasesAnimalsDisease Models, AnimalDNA-Binding ProteinsMiceMotor NeuronsPhenotypeAmino Acids, DiaminoDNA-Binding ProteinsTardbp protein, mouseALSBMAAGuamMass-spectrometryParkinsonismTDP-43

Identifiers

PMID36931113
PMCPMC12906711
OpenAlexW4321487087

What OpenQuestion holds

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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.